A Phase 1 interventional study of AdC6-HIVgp140 and AdC7-HIVgp140 in HIV Infections, sponsored by HIV Vaccine Trials Network. Completed at 6 sites in South Africa. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-12-24.
Sponsored by HIV Vaccine Trials Network · Phase 1, Interventional, and Prevention
The purpose of this study is to evaluate the safety and immunogenicity of HIV-1 vaccines based on chimpanzee serotypes of adenovirus expressing clade C gp140 and a CH505TF gp120 protein boost in healthy, HIV- uninfected adult participants.
This study will evaluate the safety and tolerability of AdC6-HIVgp140 and AdC7-HIVgp140 at doses of 1 x 10\^10 virus particles (vp) and 5 x 10\^10 vp, alone and in combination with CH505TF gp120 adjuvanted with GLA-SE in HIV- uninfected adults.
Participants will be randomly assigned to 6 groups, separated into low dose (Part A; Groups 1-3) and high dose (Part B; Groups 4-6).
Participants in Group 1 (Groups 1-3) will receive 1 x 10\^10 vp of AdC6-HIVgp140. Participants in Group 2 will receive 1 x 10\^10 vp of AdC7-HIVgp140. Participants in Group 3 will receive Placebo control.
Part A participants will undergo 6 months of scheduled clinic visits (main study) followed by AESI (Adverse Events of Special Interest) health contacts at month 12, and then annual health contacts at month 24 and 36.
Participants in Group 4 will receive 5 x 10\^10 vp of AdC6-HIVgp140 followed by 5 x 10\^10 vp of AdC7-HIVgp140 (month 3) and 400 mcg CH505TF with 10 mcg GLA-SE (month 6). Participants in Group 5 will receive 5 x 10\^10 vp of AdC7-HIVgp140 followed by 5 x 10\^10 vp of AdC6-HIVgp140 (month 3) and 400 mcg CH505TF with 10 mcg GLA-SE (month 6). Participants in Group 6 will receive Placebo control.
Part B participants (Group 4-6) will undergo 12 months of scheduled clinic visits (main study) followed by an AESI health contact at month 18, and then annual health contacts at month 24 and 36.
4,734 studies on the registry are indexed under HIV Infections; 244 are open to participants now.
This study's enrollment of 34 is below the median of 80 across 3,489 interventional studies indexed under HIV Infections.
Browse HIV Infections studies →HIV Vaccine Trials Network is the lead sponsor of 14 studies on the registry; 2 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
General and Demographic Criteria
HIV-Related Criteria
Laboratory Inclusion Values
Hemogram/Complete blood count (CBC)
For transgender participants who have been on hormone therapy for less than 6 consecutive months, determine hemoglobin eligibility based on the sex assigned at birth
Chemistry
Virology
Urine
Normal urine:
Reproductive Status
Reproductive status: A volunteer who was assigned female sex at birth must agree to use effective for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment until two months following final product administration.
Exclusion Criteria:
Vaccines and other Injections
Immune System
Volunteers who currently have, or have a history of, any condition that could be considered an AESI for the products administered in this protocol (representative examples are listed in Appendix N). The exception to Appendix N is well-controlled psoriasis, which is not exclusionary (as above)
Clinical significant medical conditions
medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
Asthma exclusion criteria: Asthma is excluded if the participant has ANY of the following:
If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined in this protocol as consistently \< 140 mm Hg systolic and \< 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be \< 140 mm Hg systolic and \< 90 mm Hg diastolic at enrollment.
If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive 1 x 10\^10 vp AdC6-HIVgp140 to be administered as two separate 1 mL IM injections into the deltoid of the non-dominant arm unless medically contraindicated at month 0.
Biological: AdC6-HIVgp140
Participants will receive 1 x 10\^10 vp AdC7-HIVgp140 to be administered as two separate 1 mL IM injections into the deltoid of the non-dominant arm unless medically contraindicated at month 0.
Biological: AdC7-HIVgp140
Participants will receive placebo for AdC6-HIVgp140 or AdC7-HIVgp140 (labeled as Sodium Chloride for Injection, 0.9%) to be administered as two separate 1 mL IM injections into the deltoid of the non-dominant arm unless medically contraindicated at month 0.
Biological: Placebo
Participants will receive 5 x 10\^10 vp AdC6-HIVgp140 to be administered as two separate 1 mL IM injections into the deltoid of the non-dominant arm unless medically contraindicated at month 0. Then 5 x 10\^10 vp AdC7-HIVgp140 to be administered as two separate 1 mL IM injections into the deltoid of the non-dominant arm unless medically contraindicated at month 3. Then 400 mcg CH505TF gp120 admixed with 10 mcg GLA-SE administered as a 1mL IM injection into either thigh unless medically contraindicated at month 6.
Biological: AdC6-HIVgp140 · Biological: AdC7-HIVgp140 · Biological: CH505TF gp120 · Biological: GLA-SE (glucopyranosyl lipid A - stable emulsion; [labeled as AP 10-201])
Participants will receive 5 x 10\^10 vp AdC7-HIVgp140 to be administered as two separate 1 mL IM injections into the deltoid of the non-dominant arm unless medically contraindicated at month 0. Then 5 x 10\^10 vp AdC6-HIVgp140 to be administered as two separate 1 mL IM injections into the deltoid of the non-dominant arm unless medically contraindicated at month 3. Then 400 mcg CH505TF gp120 admixed with 10 mcg GLA-SE administered as a 1mL IM injection into either thigh unless medically contraindicated at month 6.
Biological: AdC6-HIVgp140 · Biological: AdC7-HIVgp140 · Biological: CH505TF gp120 · Biological: GLA-SE (glucopyranosyl lipid A - stable emulsion; [labeled as AP 10-201])
Participants will receive placebo for AdC6-HIVgp140and AdC7-HIVgp140 (labeled as Sodium Chloride for Injection, 0.9%) to be administered as two separate 1 mL IM injections into the deltoid of the non-dominant arm unless medically contraindicated at month 0 and 3. Placebo for CH505TF/GLA-SE (labeled as Sodium Chloride for Injection, 0.9% ) to be administered as 1 mL IM injection into either thigh at month 6.
Biological: Placebo
The product is diluted in 2.5% Glycerol/25 mM NaCl/20 mM TRIS \[tris(hydroxymethyl)aminomethane\], pH 8.0 formulation buffer to a concentration of 1.2 x 10\^11 vp/mL and filled at 0.3 mL for AdC6-HIVgp140 into a 2 mL Type 1 glass vial and stoppered with a gray chlorobutyl rubber stopper. The product is clear to slightly cloudy liquid, essentially free of visible particles. AdC6-HIVgp140 should be stored at ≤ -65°C prior to use/preparation. The study product is described in further detail in the Investigator's Brochure (IB).
The products is diluted in 2.5% Glycerol/25 mM NaCl/20 mM TRIS \[tris(hydroxymethyl)aminomethane\], pH 8.0 formulation buffer to a concentration of 1.2 x 10\^11 vp/mL and filled at 0.6 mL for AdC7-HIVgp140 into a 2 mL Type 1 glass vial and stoppered with a gray chlorobutyl rubber stopper. The product is clear to slightly cloudy liquid, essentially free of visible particles. AdC7-HIVgp140 should be stored at ≤ -65°C prior to use/preparation. The study product is described in further detail in the IB.
CH505TF gp120 is formulated in 20 mM sodium phosphate, 150 mM NaCl, 0.02% polysorbate 80 (PS80), pH 6.5, supplied as a frozen liquid in 2 mL glass vials. Each 2 mL vial contains 0.75 mL of formulated gp120 at a concentration of 0.8 mg/mL and is stored at ≤ -65°C. The study product is described in further detail in the IB.
The GLA-SE adjuvant will be provided as vials containing 20 mcg/mL GLA in a 4% oil-in-water emulsion. Each sterile, single use vial contains 0.4 mL of product. Product appears as a milky-white liquid. GLA-SE must be stored at 2° to 8°C and must not be frozen. The study product is described in further detail within the IB.
Placebo will be Sodium Chloride for Injection, 0.9%, will be used as the placebo. It must be stored as recommended by the manufacturer.
Number of Participants Reporting Local Reactogenicity Events Signs and Symptoms: Pain and/or Tenderness
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.
Time frame: Measured through 7 days after each study product administration at Study Day 0 (Month 0) for Part A (T1, T2, and C3) and at Study Days 0 (Month 0), 84 (Month 3) and 168 (Month 6) for Part B (T4, T5, and C6).
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.
Time frame: Measured through 7 days after each study product administration at Study Day 0 (Month 0) for Part A (T1, T2, and C3) and at Study Days 0 (Month 0), 84 (Month 3) and 168 (Month 6) for Part B (T4, T5, and C6).
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.
Time frame: Measured through 7 days after each study product administration at Study Day 0 (Month 0) for Part A (T1, T2, and C3) and at Study Days 0 (Month 0), 84 (Month 3) and 168 (Month 6) for Part B (T4, T5, and C6).
Numbers of Participant With Early Study Termination Associated With Reactogenicity, AE, or Death During Main Study and AESI Visits.
From the termination and adverse event forms that were collected during main study clinical visits period and AESI contact visits. Counts are tabulated by treatment arm.
Time frame: Early study termination reason was collected through 7 days for reactogenicity, 30 days for AEs and 12 months for deaths following any receipt of study product (up to 18 months).
Number of Participants Reporting Serious Adverse Events (SAEs)
From adverse event (AE) forms, counts are tabulated by treatment arm. AE forms were collected during main study clinical visits and AESI contact visits
Time frame: Measured through 12 months following any receipt of study product(up to 18 months). Study products were given at Study Day 0 (Month 0) for Part A (T1, T2, and C3) and at Study Days 0 (Month 0), 84 (Month 3) and 168 (Month 6) for Part B (T4, T5, and C6).
Number of Participants Reporting Medically Attended Adverse Events (MAAEs)
From adverse event (AE) forms, counts are tabulated by treatment arm. AE forms were collected during main study clinical visits and AESI contact visits
Time frame: Measured through 12 months following any receipt of study product(up to 18 months). Study products were given at Study Day 0 (Month 0) for Part A (T1, T2, and C3) and at Study Days 0 (Month 0), 84 (Month 3) and 168 (Month 6) for Part B (T4, T5, and C6).
Number of Participants Reporting Adverse Event of Special Interests (AESIs)
From adverse event (AE) forms, counts are tabulated by treatment arm. AE forms were collected during main study clinical visits and AESI contact visits
Time frame: Measured through 12 months following any receipt of study product(up to 18 months). Study products were given at Study Day 0 (Month 0) for Part A (T1, T2, and C3) and at Study Days 0 (Month 0), 84 (Month 3) and 168 (Month 6) for Part B (T4, T5, and C6).
Response Rate of HIV-specific Serum IgG Binding Antibodies Assessed 4 Weeks After a Single Vaccination (Part A) or the First Vaccination (Part B)
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate). Samples from post-enrollment visits were declared to have positive responses if they met three conditions: (1) the mean fluorescence intensity (MFI) minus blank (MFI\*) values were ≥ antigen-specific cutoff at the 1:50 dilution level (based on the 95th percentile of baseline samples as calculated by SAS PROC UNIVARIATE default method, and at least 100 MFI minus blank), (2) the MFI minus blank values were greater than 3 times the baseline (day 0) MFI minus blank values, and (3) the MFI values were greater than 3 times the baseline MFI values.
Time frame: Measured at Month 1 for both Part A and Part B
Magnitude of HIV-specific Serum IgG Binding Antibodies Assessed 4 Weeks After a Single Vaccination (Part A) or the First Vaccination (Part B)
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate).
Time frame: Measured at Month 1 for both Part A and Part B
HIV-specific Serum IgG Binding Antibodies Magnitude Breadth of AUC (AUC--MB) by Panel and Treatment Arm Assessed 4 Weeks After a Single Vaccination (Part A) or the First Vaccination (Part B)
The area under the magnitude-breadth curve (AUC-MB) was calculated by first measuring the mean fluorescence intensity (MFI) of antibody binding to each antigen at 1:50 dilution. For each sample, a magnitude-breadth curve is generated by plotting the number of antigens (breadth) that exceed a series of MFI thresholds (MFI \>100). The area under this curve (AUC) is then computed by the trapezoidal rule to summarize both the strength and diversity of the antibody response in a single value, which is equivalent to the average of the log10 net MFI over the panel of antigens
Time frame: Measured at Month 1 for both Part A and Part B
Response Rate of HIV-specific CD4+ and CD8+ T-cell Responses Assessed 4 Weeks After a Single Vaccination (Part A) or the First Vaccination (Part B)
The four entries in each table were the number of cells positive for IFN-γ and/or IL-2 for both the stimulated and the negative control data. If both negative control replicates were included, then the average number of total cells and the average number of positive cells were used. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the two individual peptide pool p-values considered, using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was ≤ 0.00001, the response to the peptide pool for the T-cell subset was considered positive. If at least one peptide pool for a specific HIV-1 protein was positive, then the overall response to the protein was considered positive.
Time frame: Measured at Month 1 for both Part A and Part B
Magnitude of HIV-specific CD4+ and CD8+ T-cell by Cytokine, T-cell Subset, Antigen and Treatment Group Assessed 4 Weeks After a Single Vaccination (Part A) or the First Vaccination (Part B)
PBMC samples were stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing cytokines (IFNy and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. Reported responses magnitude for Any Env are the sum of ENV-1-PTEG-SEQ and ENV-2-PTEG-SEQ
Time frame: Measured at Month 1 for both Part A and Part B
Response Rate of Serum Neutralizing Antibodies Against Env-pseudotyped Vaccine Strains (Du422.1, Du172.17 and CH505TF) and a Tier 1A Neutralization Phenotype (MW965.26) Assessed 4 Weeks After a Single Vaccination (Part A) or the First Vaccination (Part B)
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). Response to a virus/isolate was considered positive if the neutralization titer was at or above a pre-specified cutoff of 10.
Time frame: Measured at Month 1 for both Part A and Part B
Magnitude of Serum Neutralizing Antibodies Against Env-pseudotyped Vaccine Strains (Du422.1, Du172.17 and CH505TF) and a Tier 1A Neutralization Phenotype (MW965.26) Assessed 4 Weeks After a Single Vaccination (Part A) or the First Vaccination (Part B)
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26).
Time frame: Measured at Month 1 for both Part A and Part B
Part B: Response Rate of HIV-specific Serum IgG Binding Antibodies Assessed 4 Weeks After the Second Vaccination
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate). Samples from post-enrollment visits were declared to have positive responses if they met three conditions: (1) the mean fluorescence intensity (MFI) minus blank (MFI\*) values were ≥ antigen-specific cutoff at the 1:50 dilution level (based on the 95th percentile of baseline samples as calculated by SAS PROC UNIVARIATE default method, and at least 100 MFI minus blank), (2) the MFI minus blank values were greater than 3 times the baseline (day 0) MFI minus blank values, and (3) the MFI values were greater than 3 times the baseline MFI values.
Time frame: Measured at Month 4 for Part B
Part B: Magnitude of HIV-specific Serum IgG Binding Antibodies Assessed 4 Weeks After the Second Vaccination
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate).
Time frame: Measured at Month 4 for Part B
Part B: HIV-specific Serum IgG Binding Antibodies Magnitude Breadth of AUC by Panel and Treatment Arm Assessed 4 Weeks After the Second Vaccination
The area under the magnitude-breadth curve (AUC-MB) was calculated by first measuring the mean fluorescence intensity (MFI) of antibody binding to each antigen at 1:50 dilution. For each sample, a magnitude-breadth curve is generated by plotting the number of antigens (breadth) that exceed a series of MFI thresholds (MFI \>100). The area under this curve (AUC) is then computed by the trapezoidal rule to summarize both the strength and diversity of the antibody response in a single value, which is equivalent to the average of the log10 net MFI over the panel of antigens
Time frame: Measured at Month 4 for Part B
Part B: Response Rate of HIV-specific CD4+ and CD8+ T-cell Responses Assessed 4 Weeks After the Second Vaccination
The four entries in each table were the number of cells positive for IFN-γ and/or IL-2 for both the stimulated and the negative control data. If both negative control replicates were included, then the average number of total cells and the average number of positive cells were used. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the two individual peptide pool p-values considered, using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was ≤ 0.00001, the response to the peptide pool for the T-cell subset was considered positive. If at least one peptide pool for a specific HIV-1 protein was positive, then the overall response to the protein was considered positive.
Time frame: Measured at Month 4 for Part B
Part B: Magnitude of HIV-specific CD4+ and CD8+ T-cell by Cytokine, T-cell Subset, Antigen and Treatment Group Assessed 4 Weeks After the Second Vaccination
PBMC samples were stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing cytokines (IFNy and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. Reported responses magnitude for Any Env are the sum of ENV-1-PTEG-SEQ and ENV-2-PTEG-SEQ
Time frame: Measured at Month 4 for Part B
Part B: Response Rate of Serum Neutralizing Antibodies Against Env-pseudotyped Vaccine Strains (Du422.1, Du172.17 and CH505TF) and a Tier 1A Neutralization Phenotype (MW965.26) Assessed 4 Weeks After the Second Vaccination
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). Response to a virus/isolate was considered positive if the neutralization titer was at or above a pre-specified cutoff of 10.
Time frame: Measured at Month 4 for Part B
Part B: Magnitude of Serum Neutralizing Antibodies Against Env-pseudotyped Vaccine Strains (Du422.1, Du172.17 and CH505TF) and a Tier 1A Neutralization Phenotype (MW965.26) Assessed 4 Weeks After the Second Vaccination
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). A titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only).
Time frame: Measured at Month 4 for Part B
Part B: Response Rate of HIV-specific Serum IgG Binding Antibodies Assessed 2 Weeks After the Third Vaccination
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate). Samples from post-enrollment visits were declared to have positive responses if they met three conditions: (1) the mean fluorescence intensity (MFI) minus blank (MFI\*) values were ≥ antigen-specific cutoff at the 1:50 dilution level (based on the 95th percentile of baseline samples as calculated by SAS PROC UNIVARIATE default method, and at least 100 MFI minus blank), (2) the MFI minus blank values were greater than 3 times the baseline (day 0) MFI minus blank values, and (3) the MFI values were greater than 3 times the baseline MFI values.
Time frame: Measured at Month 6.5 for Part B
Part B: Magnitude of HIV-specific Serum IgG Binding Antibodies Assessed 2 Weeks After the Third Vaccination
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate).
Time frame: Measured at Month 6.5 for Part B
Part B: HIV-specific Serum IgG Binding Antibodies Magnitude Breadth of AUC by Panel and Treatment Arm Assessed 2 Weeks After the Third Vaccination
The area under the magnitude-breadth curve (AUC-MB) was calculated by first measuring the mean fluorescence intensity (MFI) of antibody binding to each antigen at 1:50 dilution. For each sample, a magnitude-breadth curve is generated by plotting the number of antigens (breadth) that exceed a series of MFI thresholds (MFI \>100). The area under this curve (AUC) is then computed by the trapezoidal rule to summarize both the strength and diversity of the antibody response in a single value, which is equivalent to the average of the log10 net MFI over the panel of antigens
Time frame: Measured at Month 6.5 for Part B
Part B: Response Rate of HIV-specific CD4+ and CD8+ T-cell Responses Assessed 2 Weeks After the Third Vaccination
The four entries in each table were the number of cells positive for IFN-γ and/or IL-2 for both the stimulated and the negative control data. If both negative control replicates were included, then the average number of total cells and the average number of positive cells were used. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the two individual peptide pool p-values considered, using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was ≤ 0.00001, the response to the peptide pool for the T-cell subset was considered positive. If at least one peptide pool for a specific HIV-1 protein was positive, then the overall response to the protein was considered positive.
Time frame: Measured at Month 6.5 for Part B
Part B: Magnitude of HIV-specific CD4+ and CD8+ T-cell by Cytokine, T-cell Subset, Antigen and Treatment Group Assessed 2 Weeks After the Third Vaccination
PBMC samples were stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing cytokines (IFNy and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. Reported responses magnitude for Any Env are the sum of ENV-1-PTEG-SEQ and ENV-2-PTEG-SEQ
Time frame: Measured at Month 6.5 for Part B
Part B: Response Rate of Serum Neutralizing Antibodies Against Env-pseudotyped Vaccine Strains (Du422.1, Du172.17 and CH505TF) and a Tier 1A Neutralization Phenotype (MW965.26) Assessed 2 Weeks After the Third Vaccination
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). Response to a virus/isolate was considered positive if the neutralization titer was at or above a pre-specified cutoff of 10.
Time frame: Measured at Month 6.5 for Part B
Part B: Magnitude of Serum Neutralizing Antibodies Against Env-pseudotyped Vaccine Strains (Du422.1, Du172.17 and CH505TF) and a Tier 1A Neutralization Phenotype (MW965.26) Assessed 2 Weeks After the Third Vaccination
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). A titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only).
Time frame: Measured at Month 6.5 for Part B
| Milestone | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Started | 5 | 5 | 2 | 10 | 10 | 2 |
| Completed | 5 | 5 | 2 | 9 | 7 | 2 |
| Not completed | 0 | 0 | 0 | 1 | 3 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 2 | 0 |
| Withdrew: Participant unable to adhere visit schedule | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 1 | 0 |
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| None | 5 | 4 | 1 | 6 | 5 | 2 |
| Mild | 0 | 1 | 1 | 4 | 2 | 0 |
| Moderate | 0 | 0 | 0 | 0 | 3 | 0 |
| Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Erythema/Redness — None | 5 | 5 | 2 | 10 | 8 | 2 |
| Erythema/Redness — Mild | 0 | 0 | 0 | 0 | 2 | 0 |
| Erythema/Redness — Moderate | 0 | 0 | 0 | 0 | 0 | 0 |
| Erythema/Redness — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Erythema/Redness — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
| Induration/Swelling — None | 5 | 5 | 2 | 10 | 10 | 2 |
| Induration/Swelling — Mild | 0 | 0 | 0 | 0 | 0 | 0 |
| Induration/Swelling — Moderate | 0 | 0 | 0 | 0 | 0 | 0 |
| Induration/Swelling — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Induration/Swelling — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented.
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Malaise and/or fatigue — None | 5 | 5 | 2 | 6 | 7 | 1 |
| Malaise and/or fatigue — Mild | 0 | 0 | 0 | 3 | 2 | 1 |
| Malaise and/or fatigue — Moderate | 0 | 0 | 0 | 1 | 1 | 0 |
| Malaise and/or fatigue — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Malaise and/or fatigue — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
| Myalgia — None | 5 | 5 | 2 | 7 | 7 | 2 |
| Myalgia — Mild | 0 | 0 | 0 | 2 | 2 | 0 |
| Myalgia — Moderate | 0 | 0 | 0 | 1 | 1 | 0 |
| Myalgia — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Myalgia — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
| Headache — None | 5 | 3 | 2 | 7 | 5 | 2 |
| Headache — Mild | 0 | 2 | 0 | 3 | 3 | 0 |
| Headache — Moderate | 0 | 0 | 0 | 0 | 2 | 0 |
| Headache — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Headache — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
| Nausea — None | 5 | 5 | 2 | 7 | 9 | 2 |
| Nausea — Mild | 0 | 0 | 0 | 2 | 0 | 0 |
| Nausea — Moderate | 0 | 0 | 0 | 1 | 1 | 0 |
| Nausea — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Nausea — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
| Chills — None | 5 | 4 | 2 | 9 | 6 | 2 |
| Chills — Mild | 0 | 1 | 0 | 0 | 3 | 0 |
| Chills — Moderate | 0 | 0 | 0 | 1 | 1 | 0 |
| Chills — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Chills — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
| Arthralgia — None | 5 | 4 | 2 | 8 | 8 | 2 |
| Arthralgia — Mild | 0 | 1 | 0 | 1 | 0 | 0 |
| Arthralgia — Moderate | 0 | 0 | 0 | 1 | 2 | 0 |
| Arthralgia — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Arthralgia — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
| Temperature — None | 5 | 5 | 2 | 10 | 8 | 2 |
| Temperature — Mild | 0 | 0 | 0 | 0 | 2 | 0 |
| Temperature — Moderate | 0 | 0 | 0 | 0 | 0 | 0 |
| Temperature — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Temperature — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
| Max. Systemic Symptoms — None | 5 | 3 | 2 | 5 | 4 | 1 |
| Max. Systemic Symptoms — Mild | 0 | 2 | 0 | 4 | 3 | 1 |
| Max. Systemic Symptoms — Moderate | 0 | 0 | 0 | 1 | 3 | 0 |
| Max. Systemic Symptoms — Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Max. Systemic Symptoms — Potentially Life-threatening | 0 | 0 | 0 | 0 | 0 | 0 |
From the termination and adverse event forms that were collected during main study clinical visits period and AESI contact visits. Counts are tabulated by treatment arm.
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Numbers of Participant With Early Study Termination Associated With Reactogenicity, AE, or Death During Main Study and AESI Visits. | 0 | 0 | 0 | 0 | 1 | 0 |
From adverse event (AE) forms, counts are tabulated by treatment arm. AE forms were collected during main study clinical visits and AESI contact visits
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Number of Participants Reporting Serious Adverse Events (SAEs) | 0 | 0 | 0 | 0 | 1 | 0 |
From adverse event (AE) forms, counts are tabulated by treatment arm. AE forms were collected during main study clinical visits and AESI contact visits
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Number of Participants Reporting Medically Attended Adverse Events (MAAEs) | 0 | 1 | 0 | 1 | 0 | 0 |
From adverse event (AE) forms, counts are tabulated by treatment arm. AE forms were collected during main study clinical visits and AESI contact visits
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Number of Participants Reporting Adverse Event of Special Interests (AESIs) | 0 | 0 | 0 | 0 | 0 | 0 |
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate). Samples from post-enrollment visits were declared to have positive responses if they met three conditions: (1) the mean fluorescence intensity (MFI) minus blank (MFI\*) values were ≥ antigen-specific cutoff at the 1:50 dilution level (based on the 95th percentile of baseline samples as calculated by SAS PROC UNIVARIATE default method, and at least 100 MFI minus blank), (2) the MFI minus blank values were greater than 3 times the baseline (day 0) MFI minus blank values, and (3) the MFI values were greater than 3 times the baseline MFI values.
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| 1086C_D7gp120.avi/293F measured at Month 1 | 4 | 2 | 0 | 6 | 5 | 0 |
| 1394C9_G1.D11gp120.avi measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| 1428_D11gp120.avi/293F measured at Month 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| 1641A7_D11gp120.avi/293F measured at Month 1 | 0 | 0 | 0 | 3 | 1 | 0 |
| 96ZM651.D11gp120.avi measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| CAP210_D11gp120.avi/293F measured at Month 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| CAP45_D11gp120.avi/293F measured at Month 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| CH0505_CON D7gp120_avi/293F/Mon measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| CH505TF D7gp120d371_avi/293F/Mon measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| CH505TFD8N156KN160K_avi/293i Mon measured at Month 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Ce0042_D11gp120.avi/293F measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Con 6 gp120/B measured at Month 1 | 0 | 1 | 0 | 1 | 2 | 0 |
| Con S gp140 CFI measured at Month 1 | 1 | 1 | 0 | 9 | 3 | 0 |
| Du156_D11gp120.avi/293F measured at Month 1 | 1 | 0 | 0 | 7 | 2 | 0 |
| TV1c8_D11gp120.avi/293F measured at Month 1 | 1 | 0 | 0 | 8 | 2 | 0 |
| gp41 measured at Month 1 | 2 | 0 | 0 | 8 | 3 | 0 |
| gp70-001428.2.42 V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 2 | 0 |
| gp70-1012.11.TC21.3257 V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 2 | 0 |
| gp70-1051.12.C22 V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 2 | 0 |
| gp70-1394C9G1 V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 2 | 0 |
| gp70-7060101641 V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| gp70-96ZM651.02 V1v2 measured at Month 1 | 1 | 0 | 0 | 4 | 1 | 0 |
| gp70-BF1266_431a_V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 2 | 0 |
| gp70-CAP210.2.00.E8 V1V2 measured at Month 1 | 0 | 1 | 0 | 0 | 3 | 0 |
| gp70-CAP45.2.00.G3 V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| gp70-Ce1086_B2 V1V2 measured at Month 1 | 0 | 0 | 0 | 1 | 1 | 0 |
| gp70-Ce1176 V1V2 measured at Month 1 | 0 | 1 | 0 | 0 | 2 | 0 |
| gp70-Ce704010042_2ES V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| gp70-ConC V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 1 | 0 |
| gp70-Du156.12 V1V2 measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| gp70-TV1.21 V1V2 measured at Month 1 | 1 | 1 | 0 | 0 | 2 | 0 |
| gp70_CH505TF_V1V2_N156KN160K_avi/293F measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| gp70_CH505TF_V1V2_avi/293F measured at Month 1 | 0 | 0 | 0 | 0 | 1 | 0 |
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate).
| Net MFI | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| 1086C_D7gp120.avi/293F measured at Month 1 | 691.2 (435 to 907.1) | 65.8 (7.4 to 229.6) | 1 (1 to 1) | 371.8 (153.4 to 1041.7) | 164.5 (1 to 612.6) | 8.1 (4.6 to 11.7) |
| 1394C9_G1.D11gp120.avi measured at Month 1 | 3.5 (1 to 27.1) | 1.2 (1 to 2.6) | 1 (1 to 1) | 22.2 (3.2 to 35.6) | 40.9 (1 to 144.7) | 1 (1 to 1) |
| 1428_D11gp120.avi/293F measured at Month 1 | 1 (1 to 165.8) | 57.4 (16.4 to 341.9) | 1 (1 to 1) | 178.6 (122.2 to 539.3) | 3 (1 to 210.1) | 1874 (937.5 to 2810.5) |
| 1641A7_D11gp120.avi/293F measured at Month 1 | 1 (1 to 87.8) | 25.1 (1 to 52.8) | 1 (1 to 1) | 238.6 (116.8 to 921.8) | 23 (1 to 402.4) | 92.5 (46.8 to 138.2) |
| 96ZM651.D11gp120.avi measured at Month 1 | 54.8 (36.2 to 724.5) | 186.9 (82 to 2016.1) | 1 (1 to 1) | 497.1 (89.9 to 851.5) | 27 (1 to 884.4) | 1 (1 to 1) |
| CAP210_D11gp120.avi/293F measured at Month 1 | 68.6 (1 to 317.6) | 81.9 (32.7 to 438.2) | 1 (1 to 1) | 291.5 (58.6 to 469.1) | 1 (1 to 458.9) | 2725.2 (1363.1 to 4087.4) |
| CAP45_D11gp120.avi/293F measured at Month 1 | 25.4 (11.9 to 80.1) | 7.1 (2.1 to 51.2) | 1 (1 to 1) | 89.6 (61.2 to 280.8) | 41.8 (1 to 101.6) | 345.8 (173.4 to 518.1) |
| CH0505_CON D7gp120_avi/293F/Mon measured at Month 1 | 71.6 (1 to 281.5) | 336.5 (16.6 to 801.2) | 1 (1 to 1) | 137 (1 to 230) | 1 (1 to 131.9) | 3306.9 (1653.9 to 4959.8) |
| CH505TF D7gp120d371_avi/293F/Mon measured at Month 1 | 63.2 (1 to 248.2) | 347 (3.6 to 830.3) | 1 (1 to 1) | 136.1 (1 to 268.7) | 1 (1 to 60.6) | 3192 (1596.5 to 4787.5) |
| CH505TFD8N156KN160K_avi/293i Mon measured at Month 1 | 104.8 (1 to 348.7) | 292.6 (20.9 to 745.1) | 1 (1 to 1) | 124.5 (2.1 to 225.5) | 1 (1 to 206.4) | 1 (1 to 1) |
| Ce0042_D11gp120.avi/293F measured at Month 1 | 103.2 (58.3 to 205.7) | 103 (95 to 273.9) | 23.9 (12.4 to 35.3) | 167.2 (113.2 to 208.2) | 109.2 (13.8 to 229.9) | 365.6 (183.3 to 547.9) |
| Con 6 gp120/B measured at Month 1 | 38.9 (1 to 88.1) | 36.1 (4.9 to 91.8) | 1 (1 to 1) | 36.5 (8.2 to 45.3) | 1 (1 to 59.7) | 12 (6.5 to 17.5) |
| Con S gp140 CFI measured at Month 1 | 436.5 (255.8 to 1292.8) | 272.1 (23.4 to 645.4) | 8.6 (4.8 to 12.4) | 3530.2 (1597.1 to 13418.8) | 650.2 (242.9 to 3709) | 575 (312.2 to 837.8) |
| Du156_D11gp120.avi/293F measured at Month 1 | 61.9 (44.1 to 806.5) | 7.9 (1 to 16.2) | 1 (1 to 1) | 615.2 (418.6 to 1879.2) | 14 (1 to 383.9) | 62 (31.5 to 92.5) |
| TV1c8_D11gp120.avi/293F measured at Month 1 | 101.9 (11.5 to 1434) | 1 (1 to 26.8) | 1 (1 to 1) | 1227.5 (650.2 to 3362.1) | 20.6 (1 to 199.2) | 152 (76.5 to 227.5) |
| gp41 measured at Month 1 | 5349.6 (3079.3 to 11108.9) | 3582.8 (3573.8 to 3855.2) | 2214.9 (1902.8 to 2526.9) | 22000 (9936.3 to 22000) | 13128 (6580.5 to 16682.2) | 1268.5 (882.1 to 1654.9) |
| gp70-001428.2.42 V1V2 measured at Month 1 | 1 (1 to 1) | 1 (1 to 17.9) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1149.1) | 1 (1 to 1) |
| gp70-1012.11.TC21.3257 V1V2 measured at Month 1 | 1 (1 to 230.9) | 1 (1 to 22.2) | 1 (1 to 1) | 1 (1 to 1) | 79 (1 to 238.4) | 1 (1 to 1) |
| gp70-1051.12.C22 V1V2 measured at Month 1 | 1 (1 to 1) | 1 (1 to 42.9) | 1 (1 to 1) | 1 (1 to 1) | 41.6 (1 to 304.6) | 1 (1 to 1) |
| gp70-1394C9G1 V1V2 measured at Month 1 | 1 (1 to 1) | 1 (1 to 54.9) | 22.9 (11.9 to 33.8) | 1 (1 to 1) | 1 (1 to 692.1) | 1 (1 to 1) |
| gp70-7060101641 V1V2 measured at Month 1 | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 251.2) | 1 (1 to 1) |
| gp70-96ZM651.02 V1v2 measured at Month 1 | 443.5 (37.2 to 1604.8) | 2.5 (1 to 96.8) | 1 (1 to 1) | 679.8 (434.8 to 2164.2) | 365.2 (112.4 to 1161.6) | 1 (1 to 1) |
| gp70-BF1266_431a_V1V2 measured at Month 1 | 26.8 (1 to 330.1) | 1.6 (1 to 78.2) | 1 (1 to 1) | 1 (1 to 1) | 166.5 (1 to 913.2) | 1 (1 to 1) |
| gp70-CAP210.2.00.E8 V1V2 measured at Month 1 | 1 (1 to 35.4) | 65.2 (43.9 to 618.6) | 1 (1 to 1) | 1 (1 to 1) | 263.5 (66.2 to 965.2) | 1 (1 to 1) |
| gp70-CAP45.2.00.G3 V1V2 measured at Month 1 | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 636.2) | 1 (1 to 1) |
| gp70-Ce1086_B2 V1V2 measured at Month 1 | 29.9 (1 to 61.3) | 1 (1 to 251.9) | 1 (1 to 1) | 6.5 (1 to 81.5) | 1 (1 to 533) | 1 (1 to 1) |
| gp70-Ce1176 V1V2 measured at Month 1 | 1 (1 to 1) | 70.2 (13 to 360.2) | 1 (1 to 1) | 1 (1 to 1) | 232.2 (12 to 452.5) | 1 (1 to 1) |
| gp70-Ce704010042_2ES V1V2 measured at Month 1 | 1 (1 to 1) | 1 (1 to 7.2) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) |
| gp70-ConC V1V2 measured at Month 1 | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 178.4) | 1 (1 to 1) |
| gp70-Du156.12 V1V2 measured at Month 1 | 1 (1 to 1) | 1 (1 to 5.3) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) | 1 (1 to 1) |
| gp70-TV1.21 V1V2 measured at Month 1 | 1800.6 (1 to 3984.3) | 183.6 (37.2 to 1832.3) | 1 (1 to 1) | 1 (1 to 1) | 1173 (80.8 to 2925.8) | 15.8 (8.4 to 23.1) |
| gp70_CH505TF_V1V2_N156KN160K_avi/293F measured at Month 1 | 425.9 (1 to 1156) | 59.6 (1 to 1378.8) | 1 (1 to 1) | 1 (1 to 13) | 62.2 (1 to 603.9) | 79.2 (79.2 to 79.2) |
| gp70_CH505TF_V1V2_avi/293F measured at Month 1 | 1 (1 to 2274.4) | 1 (1 to 150.6) | 1 (1 to 1) | 1 (1 to 322) | 929.6 (49.1 to 2142.9) | 283.2 (283.2 to 283.2) |
The area under the magnitude-breadth curve (AUC-MB) was calculated by first measuring the mean fluorescence intensity (MFI) of antibody binding to each antigen at 1:50 dilution. For each sample, a magnitude-breadth curve is generated by plotting the number of antigens (breadth) that exceed a series of MFI thresholds (MFI \>100). The area under this curve (AUC) is then computed by the trapezoidal rule to summarize both the strength and diversity of the antibody response in a single value, which is equivalent to the average of the log10 net MFI over the panel of antigens
| log10(net MFI) | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Clade C gp120 measured at Month 1 | 2 (2 to 2.08) | 2 (2 to 2) | 2 (2 to 2) | 2.19 (2.14 to 2.37) | 2 (2 to 2.09) | 2 (2 to 2) |
| Clade C gp70 V1V2 measured at Month 1 | 2.05 (2 to 2.11) | 2 (2 to 2.07) | 2 (2 to 2) | 2 (2 to 2.12) | 2.12 (2.03 to 2.18) | 2 (2 to 2) |
The four entries in each table were the number of cells positive for IFN-γ and/or IL-2 for both the stimulated and the negative control data. If both negative control replicates were included, then the average number of total cells and the average number of positive cells were used. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the two individual peptide pool p-values considered, using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was ≤ 0.00001, the response to the peptide pool for the T-cell subset was considered positive. If at least one peptide pool for a specific HIV-1 protein was positive, then the overall response to the protein was considered positive.
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Any Env for CD4+ T Cells, measured at Month 1 | 1 | 3 | 0 | 3 | 7 | 0 |
| Any Env for CD8+ T Cells, measured at Month 1 | 1 | 2 | 1 | 5 | 5 | 0 |
| ENV-1-PTEG-SEQ for CD4+ T Cells, measured at Month 1 | 0 | 3 | 0 | 0 | 6 | 0 |
| ENV-1-PTEG-SEQ for CD8+ T Cells, measured at Month 1 | 1 | 2 | 1 | 4 | 4 | 0 |
| ENV-2-PTEG-SEQ for CD4+ T Cells, measured at Month 1 | 1 | 2 | 0 | 3 | 6 | 0 |
| ENV-2-PTEG-SEQ for CD8+ T Cells, measured at Month 1 | 0 | 1 | 0 | 1 | 4 | 0 |
PBMC samples were stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing cytokines (IFNy and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. Reported responses magnitude for Any Env are the sum of ENV-1-PTEG-SEQ and ENV-2-PTEG-SEQ
| Percentage of cells | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Any Env for CD4+ T Cells, measured at Month 1 | 0.019 (0.005 to 0.043) | 0.103 (0.096 to 0.119) | 0.001 (0.001 to 0.001) | 0.028 (0.001 to 0.055) | 0.13 (0.053 to 0.162) | 0.011 (0.006 to 0.017) |
| Any Env for CD8+ T Cells, measured at Month 1 | 0.011 (0.001 to 0.022) | 0.096 (0.035 to 0.189) | 0.028 (0.016 to 0.041) | 0.044 (0.007 to 0.091) | 0.067 (0.041 to 0.126) | 0.025 (0.021 to 0.029) |
| ENV-1-PTEG-SEQ for CD4+ T Cells, measured at Month 1 | 0.008 (0.005 to 0.015) | 0.066 (0.047 to 0.084) | 0.001 (0.001 to 0.001) | 0.008 (0.001 to 0.019) | 0.047 (0.025 to 0.064) | 0.011 (0.006 to 0.016) |
| ENV-1-PTEG-SEQ for CD8+ T Cells, measured at Month 1 | 0.011 (0.001 to 0.022) | 0.038 (0.025 to 0.11) | 0.017 (0.01 to 0.024) | 0.028 (0.007 to 0.033) | 0.033 (0.021 to 0.094) | 0.016 (0.009 to 0.022) |
| ENV-2-PTEG-SEQ for CD4+ T Cells, measured at Month 1 | 0.011 (0.001 to 0.028) | 0.049 (0.037 to 0.058) | 0.001 (0.001 to 0.001) | 0.019 (0.001 to 0.036) | 0.065 (0.032 to 0.093) | 0.001 (0.001 to 0.001) |
| ENV-2-PTEG-SEQ for CD8+ T Cells, measured at Month 1 | 0.001 (0.001 to 0.001) | 0.011 (0.007 to 0.035) | 0.012 (0.006 to 0.017) | 0.014 (0.001 to 0.023) | 0.023 (0.011 to 0.048) | 0.009 (0.006 to 0.012) |
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). Response to a virus/isolate was considered positive if the neutralization titer was at or above a pre-specified cutoff of 10.
| Participants | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| CH505TF at dilution 50, measured at Month 1 | 0 | 1 | 0 | 1 | 0 | 0 |
| CH505TF at dilution 80, measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| DU172.17 at dilution 50, measured at Month 1 | 0 | 0 | 0 | 2 | 0 | 0 |
| DU172.17 at dilution 80, measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Du422.1 at dilution 50, measured at Month 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Du422.1 at dilution 80, measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| MW965.26 at dilution 50, measured at Month 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| MW965.26 at dilution 80, measured at Month 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26).
| titer | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| CH505TF at dilution 50, measured at Month 1 | 5 (5 to 5) | 5 (5 to 7.1) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| CH505TF at dilution 80, measured at Month 1 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| DU172.17 at dilution 50, measured at Month 1 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| DU172.17 at dilution 80, measured at Month 1 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| Du422.1 at dilution 50, measured at Month 1 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| Du422.1 at dilution 80, measured at Month 1 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| MW965.26 at dilution 50, measured at Month 1 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| MW965.26 at dilution 80, measured at Month 1 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate). Samples from post-enrollment visits were declared to have positive responses if they met three conditions: (1) the mean fluorescence intensity (MFI) minus blank (MFI\*) values were ≥ antigen-specific cutoff at the 1:50 dilution level (based on the 95th percentile of baseline samples as calculated by SAS PROC UNIVARIATE default method, and at least 100 MFI minus blank), (2) the MFI minus blank values were greater than 3 times the baseline (day 0) MFI minus blank values, and (3) the MFI values were greater than 3 times the baseline MFI values.
| Participants | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| 1086C_D7gp120.avi/293F measured at Month 4 | 9 | 7 | 0 |
| 1394C9_G1.D11gp120.avi measured at Month 4 | 4 | 2 | 0 |
| 1428_D11gp120.avi/293F measured at Month 4 | 7 | 4 | 0 |
| 1641A7_D11gp120.avi/293F measured at Month 4 | 8 | 6 | 0 |
| 96ZM651.D11gp120.avi measured at Month 4 | 6 | 3 | 0 |
| CAP210_D11gp120.avi/293F measured at Month 4 | 5 | 3 | 0 |
| CAP45_D11gp120.avi/293F measured at Month 4 | 6 | 3 | 0 |
| CH0505_CON D7gp120_avi/293F/Mon measured at Month 4 | 5 | 2 | 0 |
| CH505TF D7gp120d371_avi/293F/Mon measured at Month 4 | 6 | 2 | 0 |
| CH505TFD8N156KN160K_avi/293i Mon measured at Month 4 | 6 | 3 | 0 |
| Ce0042_D11gp120.avi/293F measured at Month 4 | 3 | 2 | 0 |
| Con 6 gp120/B measured at Month 4 | 8 | 6 | 0 |
| Con S gp140 CFI measured at Month 4 | 9 | 7 | 0 |
| Du156_D11gp120.avi/293F measured at Month 4 | 9 | 6 | 0 |
| TV1c8_D11gp120.avi/293F measured at Month 4 | 9 | 7 | 0 |
| gp41 measured at Month 4 | 8 | 5 | 0 |
| gp70-001428.2.42 V1V2 measured at Month 4 | 0 | 1 | 0 |
| gp70-1012.11.TC21.3257 V1V2 measured at Month 4 | 2 | 3 | 0 |
| gp70-1051.12.C22 V1V2 measured at Month 4 | 1 | 4 | 0 |
| gp70-1394C9G1 V1V2 measured at Month 4 | 0 | 3 | 0 |
| gp70-7060101641 V1V2 measured at Month 4 | 0 | 1 | 0 |
| gp70-96ZM651.02 V1v2 measured at Month 4 | 2 | 2 | 0 |
| gp70-BF1266_431a_V1V2 measured at Month 4 | 0 | 2 | 0 |
| gp70-CAP210.2.00.E8 V1V2 measured at Month 4 | 0 | 3 | 0 |
| gp70-CAP45.2.00.G3 V1V2 measured at Month 4 | 0 | 1 | 0 |
| gp70-Ce1086_B2 V1V2 measured at Month 4 | 0 | 1 | 0 |
| gp70-Ce1176 V1V2 measured at Month 4 | 0 | 2 | 0 |
| gp70-Ce704010042_2ES V1V2 measured at Month 4 | 0 | 1 | 0 |
| gp70-ConC V1V2 measured at Month 4 | 0 | 1 | 0 |
| gp70-Du156.12 V1V2 measured at Month 4 | 0 | 1 | 0 |
| gp70-TV1.21 V1V2 measured at Month 4 | 0 | 2 | 0 |
| gp70_CH505TF_V1V2_N156KN160K_avi/293F measured at Month 4 | 0 | 1 | 0 |
| gp70_CH505TF_V1V2_avi/293F measured at Month 4 | 0 | 1 | 0 |
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate).
| Net MFI | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| 1086C_D7gp120.avi/293F measured at Month 4 | 7160.2 (2493 to 22000) | 5318.9 (1591.6 to 22000) | 15.2 (8.1 to 22.4) |
| 1394C9_G1.D11gp120.avi measured at Month 4 | 287.2 (189.2 to 1066.5) | 168.6 (99.9 to 2388.9) | 1 (1 to 1) |
| 1428_D11gp120.avi/293F measured at Month 4 | 1886 (1202.5 to 11290) | 1826.8 (453.2 to 12090) | 2131.1 (1066.1 to 3196.2) |
| 1641A7_D11gp120.avi/293F measured at Month 4 | 2174.2 (1228 to 13183.5) | 2312.1 (673.7 to 22000) | 104.5 (52.8 to 156.2) |
| 96ZM651.D11gp120.avi measured at Month 4 | 3297.8 (884.5 to 8019) | 844.8 (657.5 to 12190.2) | 1 (1 to 1) |
| CAP210_D11gp120.avi/293F measured at Month 4 | 1553 (502.5 to 9846.8) | 437.5 (250.4 to 11716) | 3179.5 (1590.2 to 4768.8) |
| CAP45_D11gp120.avi/293F measured at Month 4 | 595.5 (386 to 3380.2) | 653.6 (251.8 to 11100.8) | 388.6 (194.8 to 582.4) |
| CH0505_CON D7gp120_avi/293F/Mon measured at Month 4 | 1790.2 (359.2 to 3655.2) | 355 (242.1 to 11501.5) | 3982.1 (1991.6 to 5972.7) |
| CH505TF D7gp120d371_avi/293F/Mon measured at Month 4 | 1589.8 (289.5 to 4195.2) | 340.2 (184.2 to 11551.4) | 3744.6 (1872.8 to 5616.4) |
| CH505TFD8N156KN160K_avi/293i Mon measured at Month 4 | 1826.2 (356 to 3587.5) | 364 (218 to 10714.8) | 1 (1 to 1) |
| Ce0042_D11gp120.avi/293F measured at Month 4 | 561.2 (161 to 1006.5) | 207 (174.8 to 4715.1) | 457 (229 to 685) |
| Con 6 gp120/B measured at Month 4 | 889 (491.2 to 4699.8) | 979.9 (94.2 to 6685.2) | 27.5 (14.2 to 40.8) |
| Con S gp140 CFI measured at Month 4 | 22000 (19531.5 to 22000) | 22000 (22000 to 22000) | 654.1 (337.1 to 971.2) |
| Du156_D11gp120.avi/293F measured at Month 4 | 3444.8 (2452.5 to 21158) | 5790.4 (1533.3 to 20619.8) | 84.4 (42.7 to 126.1) |
| TV1c8_D11gp120.avi/293F measured at Month 4 | 5688.5 (3846 to 22000) | 9944.1 (1892.9 to 22000) | 197.8 (99.4 to 296.1) |
| gp41 measured at Month 4 | 22000 (22000 to 22000) | 22000 (22000 to 22000) | 1532.9 (1025.3 to 2040.4) |
| gp70-001428.2.42 V1V2 measured at Month 4 | 1 (1 to 20.2) | 83.2 (1 to 2134.5) | 1 (1 to 1) |
| gp70-1012.11.TC21.3257 V1V2 measured at Month 4 | 31.5 (1 to 103.9) | 194.2 (98.3 to 676.2) | 13.8 (7.4 to 20.1) |
| gp70-1051.12.C22 V1V2 measured at Month 4 | 1 (1 to 34.2) | 295.5 (52.9 to 679.5) | 1 (1 to 1) |
| gp70-1394C9G1 V1V2 measured at Month 4 | 7.5 (1 to 79.9) | 188.5 (1 to 4973.2) | 1 (1 to 1) |
| gp70-7060101641 V1V2 measured at Month 4 | 1 (1 to 9.5) | 1 (1 to 1485) | 1 (1 to 1) |
| gp70-96ZM651.02 V1v2 measured at Month 4 | 447 (83.1 to 1022.8) | 609.8 (270.4 to 3245.8) | 1 (1 to 1) |
| gp70-BF1266_431a_V1V2 measured at Month 4 | 1 (1 to 97.2) | 107.8 (18.8 to 3505.3) | 1 (1 to 1) |
| gp70-CAP210.2.00.E8 V1V2 measured at Month 4 | 1 (1 to 1) | 167.8 (39.2 to 1172) | 1 (1 to 1) |
| gp70-CAP45.2.00.G3 V1V2 measured at Month 4 | 1 (1 to 5.9) | 84.5 (1 to 1412.5) | 1 (1 to 1) |
| gp70-Ce1086_B2 V1V2 measured at Month 4 | 157.9 (92 to 246.5) | 219.8 (16.6 to 4753.5) | 1 (1 to 1) |
| gp70-Ce1176 V1V2 measured at Month 4 | 1 (1 to 1) | 114.8 (8.4 to 1575.8) | 1 (1 to 1) |
| gp70-Ce704010042_2ES V1V2 measured at Month 4 | 1 (1 to 1) | 1 (1 to 358.1) | 1 (1 to 1) |
| gp70-ConC V1V2 measured at Month 4 | 1 (1 to 1) | 3 (1 to 1500) | 1 (1 to 1) |
| gp70-Du156.12 V1V2 measured at Month 4 | 1 (1 to 2.7) | 1 (1 to 12.1) | 1 (1 to 1) |
| gp70-TV1.21 V1V2 measured at Month 4 | 42.1 (1 to 59.5) | 331.6 (1 to 3697.9) | 14.2 (7.6 to 20.9) |
| gp70_CH505TF_V1V2_N156KN160K_avi/293F measured at Month 4 | 1 (1 to 1) | 244 (50.2 to 461.6) | 93.8 (93.8 to 93.8) |
| gp70_CH505TF_V1V2_avi/293F measured at Month 4 | 1 (1 to 79.7) | 1463 (342.8 to 1770.2) | 307.8 (307.8 to 307.8) |
The area under the magnitude-breadth curve (AUC-MB) was calculated by first measuring the mean fluorescence intensity (MFI) of antibody binding to each antigen at 1:50 dilution. For each sample, a magnitude-breadth curve is generated by plotting the number of antigens (breadth) that exceed a series of MFI thresholds (MFI \>100). The area under this curve (AUC) is then computed by the trapezoidal rule to summarize both the strength and diversity of the antibody response in a single value, which is equivalent to the average of the log10 net MFI over the panel of antigens
| log10(net MFI) | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| Clade C gp120 measured at Month 4 | 2.94 (2.51 to 3.84) | 2.64 (2.21 to 3.61) | 2 (2 to 2) |
| Clade C gp70 V1V2 measured at Month 4 | 2 (2 to 2.04) | 2.05 (2.01 to 2.45) | 2 (2 to 2) |
The four entries in each table were the number of cells positive for IFN-γ and/or IL-2 for both the stimulated and the negative control data. If both negative control replicates were included, then the average number of total cells and the average number of positive cells were used. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the two individual peptide pool p-values considered, using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was ≤ 0.00001, the response to the peptide pool for the T-cell subset was considered positive. If at least one peptide pool for a specific HIV-1 protein was positive, then the overall response to the protein was considered positive.
| Participants | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| Any Env for CD4+ T Cells, measured at Month 4 | 3 | 6 | 0 |
| Any Env for CD8+ T Cells, measured at Month 4 | 5 | 5 | 0 |
| ENV-1-PTEG-SEQ for CD4+ T Cells, measured at Month 4 | 3 | 6 | 0 |
| ENV-1-PTEG-SEQ for CD8+ T Cells, measured at Month 4 | 5 | 5 | 0 |
| ENV-2-PTEG-SEQ for CD4+ T Cells, measured at Month 4 | 3 | 4 | 0 |
| ENV-2-PTEG-SEQ for CD8+ T Cells, measured at Month 4 | 4 | 5 | 0 |
PBMC samples were stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing cytokines (IFNy and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. Reported responses magnitude for Any Env are the sum of ENV-1-PTEG-SEQ and ENV-2-PTEG-SEQ
| Percentage of cells | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| Any Env for CD4+ T Cells, measured at Month 4 | 0.049 (0.038 to 0.156) | 0.09 (0.046 to 0.105) | 0.009 (0.008 to 0.009) |
| Any Env for CD8+ T Cells, measured at Month 4 | 0.091 (0.012 to 0.154) | 0.11 (0.046 to 0.319) | 0.011 (0.011 to 0.012) |
| ENV-1-PTEG-SEQ for CD4+ T Cells, measured at Month 4 | 0.031 (0.019 to 0.052) | 0.046 (0.032 to 0.05) | 0.004 (0.003 to 0.006) |
| ENV-1-PTEG-SEQ for CD8+ T Cells, measured at Month 4 | 0.043 (0.011 to 0.081) | 0.074 (0.033 to 0.135) | 0.005 (0.003 to 0.007) |
| ENV-2-PTEG-SEQ for CD4+ T Cells, measured at Month 4 | 0.024 (0.019 to 0.108) | 0.04 (0.018 to 0.055) | 0.005 (0.003 to 0.007) |
| ENV-2-PTEG-SEQ for CD8+ T Cells, measured at Month 4 | 0.011 (0.006 to 0.074) | 0.03 (0.015 to 0.111) | 0.006 (0.004 to 0.009) |
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). Response to a virus/isolate was considered positive if the neutralization titer was at or above a pre-specified cutoff of 10.
| Participants | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| CH505TF at dilution 50, measured at Month 4 | 0 | 0 | 1 |
| CH505TF at dilution 80, measured at Month 4 | 0 | 0 | 0 |
| DU172.17 at dilution 50, measured at Month 4 | 0 | 0 | 1 |
| DU172.17 at dilution 80, measured at Month 4 | 0 | 0 | 0 |
| Du422.1 at dilution 50, measured at Month 4 | 0 | 0 | 1 |
| Du422.1 at dilution 80, measured at Month 4 | 0 | 0 | 0 |
| MW965.26 at dilution 50, measured at Month 4 | 8 | 6 | 0 |
| MW965.26 at dilution 80, measured at Month 4 | 5 | 5 | 0 |
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). A titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only).
| titer | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| CH505TF at dilution 50, measured at Month 4 | 5 (5 to 5) | 5 (5 to 5) | 9.5 (7.2 to 11.7) |
| CH505TF at dilution 80, measured at Month 4 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| DU172.17 at dilution 50, measured at Month 4 | 5 (5 to 5) | 5 (5 to 5) | 7.8 (6.4 to 9.2) |
| DU172.17 at dilution 80, measured at Month 4 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| Du422.1 at dilution 50, measured at Month 4 | 5 (5 to 5) | 5 (5 to 5) | 9.9 (7.5 to 12.4) |
| Du422.1 at dilution 80, measured at Month 4 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| MW965.26 at dilution 50, measured at Month 4 | 79.2 (33.8 to 94) | 71 (12.1 to 109.8) | 5 (5 to 5) |
| MW965.26 at dilution 80, measured at Month 4 | 14.6 (5 to 32.9) | 14.7 (5 to 23.5) | 5 (5 to 5) |
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate). Samples from post-enrollment visits were declared to have positive responses if they met three conditions: (1) the mean fluorescence intensity (MFI) minus blank (MFI\*) values were ≥ antigen-specific cutoff at the 1:50 dilution level (based on the 95th percentile of baseline samples as calculated by SAS PROC UNIVARIATE default method, and at least 100 MFI minus blank), (2) the MFI minus blank values were greater than 3 times the baseline (day 0) MFI minus blank values, and (3) the MFI values were greater than 3 times the baseline MFI values.
| Participants | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| 1086C_D7gp120.avi/293F measured at Month 6.5 | 8 | 7 | 0 |
| 1394C9_G1.D11gp120.avi measured at Month 6.5 | 8 | 7 | 0 |
| 1428_D11gp120.avi/293F measured at Month 6.5 | 8 | 6 | 0 |
| 1641A7_D11gp120.avi/293F measured at Month 6.5 | 8 | 7 | 0 |
| 96ZM651.D11gp120.avi measured at Month 6.5 | 8 | 6 | 0 |
| CAP210_D11gp120.avi/293F measured at Month 6.5 | 8 | 6 | 0 |
| CAP45_D11gp120.avi/293F measured at Month 6.5 | 8 | 7 | 0 |
| CH0505_CON D7gp120_avi/293F/Mon measured at Month 6.5 | 8 | 6 | 0 |
| CH505TF D7gp120d371_avi/293F/Mon measured at Month 6.5 | 8 | 6 | 0 |
| CH505TFD8N156KN160K_avi/293i Mon measured at Month 6.5 | 8 | 6 | 0 |
| Ce0042_D11gp120.avi/293F measured at Month 6.5 | 8 | 6 | 0 |
| Con 6 gp120/B measured at Month 6.5 | 8 | 7 | 0 |
| Con S gp140 CFI measured at Month 6.5 | 8 | 7 | 0 |
| Du156_D11gp120.avi/293F measured at Month 6.5 | 8 | 7 | 0 |
| TV1c8_D11gp120.avi/293F measured at Month 6.5 | 8 | 7 | 0 |
| gp41 measured at Month 6.5 | 7 | 4 | 0 |
| gp70-001428.2.42 V1V2 measured at Month 6.5 | 3 | 3 | 0 |
| gp70-1012.11.TC21.3257 V1V2 measured at Month 6.5 | 4 | 3 | 0 |
| gp70-1051.12.C22 V1V2 measured at Month 6.5 | 3 | 4 | 0 |
| gp70-1394C9G1 V1V2 measured at Month 6.5 | 4 | 4 | 0 |
| gp70-7060101641 V1V2 measured at Month 6.5 | 3 | 2 | 0 |
| gp70-96ZM651.02 V1v2 measured at Month 6.5 | 2 | 2 | 0 |
| gp70-BF1266_431a_V1V2 measured at Month 6.5 | 3 | 3 | 0 |
| gp70-CAP210.2.00.E8 V1V2 measured at Month 6.5 | 2 | 4 | 0 |
| gp70-CAP45.2.00.G3 V1V2 measured at Month 6.5 | 3 | 2 | 0 |
| gp70-Ce1086_B2 V1V2 measured at Month 6.5 | 3 | 3 | 0 |
| gp70-Ce1176 V1V2 measured at Month 6.5 | 1 | 2 | 0 |
| gp70-Ce704010042_2ES V1V2 measured at Month 6.5 | 1 | 1 | 0 |
| gp70-ConC V1V2 measured at Month 6.5 | 2 | 1 | 0 |
| gp70-Du156.12 V1V2 measured at Month 6.5 | 0 | 1 | 0 |
| gp70-TV1.21 V1V2 measured at Month 6.5 | 1 | 2 | 0 |
| gp70_CH505TF_V1V2_N156KN160K_avi/293F measured at Month 6.5 | 2 | 2 | 0 |
| gp70_CH505TF_V1V2_avi/293F measured at Month 6.5 | 3 | 2 | 0 |
Serum HIV-1-specific IgG responses (dilution 1:50) against gp120, gp140, gp70-V1V2 and gp41 antigens were measured on a Bio-Plex instrument (Bio-Rad) using a standardized custom HIV-1 Luminex assay. The readout was background-subtracted mean fluorescence intensity (MFI), where background referred to a plate level control (i.e., a blank well run on each plate).
| Net MFI | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| 1086C_D7gp120.avi/293F measured at Month 6.5 | 22000 (22000 to 22000) | 22000 (22000 to 22000) | 13.5 (7.2 to 19.8) |
| 1394C9_G1.D11gp120.avi measured at Month 6.5 | 20251.9 (4882.5 to 22000) | 5330.2 (3441.4 to 11133.6) | 6 (3.5 to 8.5) |
| 1428_D11gp120.avi/293F measured at Month 6.5 | 22000 (18414.2 to 22000) | 22000 (12803.9 to 22000) | 1499.4 (750.2 to 2248.6) |
| 1641A7_D11gp120.avi/293F measured at Month 6.5 | 22000 (18493.9 to 22000) | 22000 (15769.4 to 22000) | 70.5 (35.8 to 105.2) |
| 96ZM651.D11gp120.avi measured at Month 6.5 | 22000 (21971.9 to 22000) | 22000 (22000 to 22000) | 1 (1 to 1) |
| CAP210_D11gp120.avi/293F measured at Month 6.5 | 22000 (19094.1 to 22000) | 22000 (14543.1 to 22000) | 2226.2 (1113.6 to 3338.9) |
| CAP45_D11gp120.avi/293F measured at Month 6.5 | 22000 (12319.1 to 22000) | 13516.5 (7494 to 22000) | 234.4 (118.9 to 349.8) |
| CH0505_CON D7gp120_avi/293F/Mon measured at Month 6.5 | 22000 (20718.1 to 22000) | 22000 (16872.2 to 22000) | 2943.4 (1472.2 to 4414.6) |
| CH505TF D7gp120d371_avi/293F/Mon measured at Month 6.5 | 22000 (18795.9 to 22000) | 22000 (12295 to 22000) | 2626.6 (1313.8 to 3939.4) |
| CH505TFD8N156KN160K_avi/293i Mon measured at Month 6.5 | 22000 (21365.8 to 22000) | 22000 (17977.8 to 22000) | 1 (1 to 1) |
| Ce0042_D11gp120.avi/293F measured at Month 6.5 | 22000 (9925.1 to 22000) | 11018.1 (4555.2 to 13940.2) | 314.5 (157.8 to 471.2) |
| Con 6 gp120/B measured at Month 6.5 | 22000 (18092.1 to 22000) | 21599.8 (12923.9 to 22000) | 6.9 (3.9 to 9.8) |
| Con S gp140 CFI measured at Month 6.5 | 22000 (22000 to 22000) | 22000 (22000 to 22000) | 417.6 (213.3 to 621.9) |
| Du156_D11gp120.avi/293F measured at Month 6.5 | 22000 (20249.4 to 22000) | 22000 (20090.5 to 22000) | 55.6 (28.3 to 82.9) |
| TV1c8_D11gp120.avi/293F measured at Month 6.5 | 22000 (22000 to 22000) | 22000 (22000 to 22000) | 113.9 (57.4 to 170.3) |
| gp41 measured at Month 6.5 | 11919.2 (9853.8 to 16697.5) | 22000 (22000 to 22000) | 1415.2 (1396.4 to 1434.1) |
| gp70-001428.2.42 V1V2 measured at Month 6.5 | 81.8 (22.5 to 360.5) | 496 (63 to 4034.8) | 1 (1 to 1) |
| gp70-1012.11.TC21.3257 V1V2 measured at Month 6.5 | 344 (13.1 to 1232.2) | 601.8 (290.8 to 1328.8) | 1 (1 to 1) |
| gp70-1051.12.C22 V1V2 measured at Month 6.5 | 283.2 (1 to 635.9) | 399.8 (180.2 to 3368.8) | 1 (1 to 1) |
| gp70-1394C9G1 V1V2 measured at Month 6.5 | 1375.8 (155.2 to 7640) | 1141.5 (135.1 to 10074.1) | 1 (1 to 1) |
| gp70-7060101641 V1V2 measured at Month 6.5 | 126.5 (1 to 2443.9) | 196.6 (123.2 to 4280.2) | 1.9 (1.4 to 2.3) |
| gp70-96ZM651.02 V1v2 measured at Month 6.5 | 614.8 (256.6 to 8476.2) | 1780.1 (143.4 to 3878.1) | 1 (1 to 1) |
| gp70-BF1266_431a_V1V2 measured at Month 6.5 | 1508.5 (19.1 to 1705.4) | 491.2 (228.2 to 9834.2) | 1 (1 to 1) |
| gp70-CAP210.2.00.E8 V1V2 measured at Month 6.5 | 1 (1 to 222.8) | 1032.4 (69.9 to 2225.6) | 1 (1 to 1) |
| gp70-CAP45.2.00.G3 V1V2 measured at Month 6.5 | 1 (1 to 556.4) | 89.9 (8.2 to 3034.1) | 1 (1 to 1) |
| gp70-Ce1086_B2 V1V2 measured at Month 6.5 | 262.5 (88.2 to 6151.6) | 864.4 (325.9 to 9912.2) | 1 (1 to 1) |
| gp70-Ce1176 V1V2 measured at Month 6.5 | 1 (1 to 18) | 572.9 (13.6 to 1937.1) | 1 (1 to 1) |
| gp70-Ce704010042_2ES V1V2 measured at Month 6.5 | 1 (1 to 1) | 1 (1 to 2029.6) | 1 (1 to 1) |
| gp70-ConC V1V2 measured at Month 6.5 | 66.8 (1 to 163.5) | 161.8 (42.2 to 2484.6) | 1 (1 to 1) |
| gp70-Du156.12 V1V2 measured at Month 6.5 | 1 (1 to 1) | 1 (1 to 88.2) | 7.2 (4.1 to 10.4) |
| gp70-TV1.21 V1V2 measured at Month 6.5 | 863 (214.1 to 1447) | 694 (278.2 to 7141.5) | 1 (1 to 1) |
| gp70_CH505TF_V1V2_N156KN160K_avi/293F measured at Month 6.5 | 623.8 (1 to 2979.4) | 445.8 (423.8 to 1988.2) | 71 (71 to 71) |
| gp70_CH505TF_V1V2_avi/293F measured at Month 6.5 | 1721.8 (28.9 to 11673.6) | 2548 (1283 to 6476.8) | 286.5 (286.5 to 286.5) |
The area under the magnitude-breadth curve (AUC-MB) was calculated by first measuring the mean fluorescence intensity (MFI) of antibody binding to each antigen at 1:50 dilution. For each sample, a magnitude-breadth curve is generated by plotting the number of antigens (breadth) that exceed a series of MFI thresholds (MFI \>100). The area under this curve (AUC) is then computed by the trapezoidal rule to summarize both the strength and diversity of the antibody response in a single value, which is equivalent to the average of the log10 net MFI over the panel of antigens
| log10(net MFI) | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| Clade C gp120 measured at Month 6.5 | 4.34 (4.16 to 4.34) | 4.22 (4.01 to 4.26) | 2 (2 to 2) |
| Clade C gp70 V1V2 measured at Month 6.5 | 2.33 (2.08 to 2.56) | 2.22 (2.08 to 2.9) | 2 (2 to 2) |
The four entries in each table were the number of cells positive for IFN-γ and/or IL-2 for both the stimulated and the negative control data. If both negative control replicates were included, then the average number of total cells and the average number of positive cells were used. A one-sided Fisher's exact test was applied to the table, testing whether the number of cytokine-producing cells for the stimulated data was equal to that for the negative control data. Since multiple individual tests (for each peptide pool) were conducted simultaneously, a multiplicity adjustment was made to the two individual peptide pool p-values considered, using the Bonferroni-Holm adjustment method. If the adjusted p-value for a peptide pool was ≤ 0.00001, the response to the peptide pool for the T-cell subset was considered positive. If at least one peptide pool for a specific HIV-1 protein was positive, then the overall response to the protein was considered positive.
| Participants | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| Any Env for CD4+ T Cells, measured at Month 6.5 | 7 | 6 | 0 |
| Any Env for CD8+ T Cells, measured at Month 6.5 | 6 | 5 | 0 |
| ENV-1-PTEG-SEQ for CD4+ T Cells, measured at Month 6.5 | 7 | 6 | 0 |
| ENV-1-PTEG-SEQ for CD8+ T Cells, measured at Month 6.5 | 6 | 5 | 0 |
| ENV-2-PTEG-SEQ for CD4+ T Cells, measured at Month 6.5 | 5 | 6 | 0 |
| ENV-2-PTEG-SEQ for CD8+ T Cells, measured at Month 6.5 | 3 | 3 | 0 |
PBMC samples were stimulated with synthetic peptide pools or left unstimulated as a negative control. For each sample, T-cell subset, and peptide pool, response magnitude is % cells expressing cytokines (IFNy and/or IL-2) after peptide stimulation minus % cells expressing markers after no stimulation. Reported responses magnitude for Any Env are the sum of ENV-1-PTEG-SEQ and ENV-2-PTEG-SEQ
| Percentage of cells | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| Any Env for CD4+ T Cells, measured at Month 6.5 | 0.172 (0.077 to 0.278) | 0.257 (0.119 to 0.313) | 0.007 (0.004 to 0.011) |
| Any Env for CD8+ T Cells, measured at Month 6.5 | 0.067 (0.038 to 0.113) | 0.094 (0.041 to 0.25) | 0.002 (0.001 to 0.002) |
| ENV-1-PTEG-SEQ for CD4+ T Cells, measured at Month 6.5 | 0.1 (0.068 to 0.166) | 0.158 (0.081 to 0.195) | 0.007 (0.004 to 0.011) |
| ENV-1-PTEG-SEQ for CD8+ T Cells, measured at Month 6.5 | 0.059 (0.027 to 0.078) | 0.065 (0.026 to 0.118) | 0.002 (0.001 to 0.002) |
| ENV-2-PTEG-SEQ for CD4+ T Cells, measured at Month 6.5 | 0.072 (0.014 to 0.095) | 0.071 (0.051 to 0.132) | 0.001 (0.001 to 0.001) |
| ENV-2-PTEG-SEQ for CD8+ T Cells, measured at Month 6.5 | 0.012 (0.007 to 0.036) | 0.03 (0.015 to 0.085) | 0.001 (0.001 to 0.001) |
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). Response to a virus/isolate was considered positive if the neutralization titer was at or above a pre-specified cutoff of 10.
| Participants | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| CH505TF at dilution 50, measured at Month 6.5 | 1 | 2 | 0 |
| CH505TF at dilution 80, measured at Month 6.5 | 1 | 0 | 0 |
| DU172.17 at dilution 50, measured at Month 6.5 | 2 | 0 | 0 |
| DU172.17 at dilution 80, measured at Month 6.5 | 0 | 0 | 0 |
| Du422.1 at dilution 50, measured at Month 6.5 | 1 | 1 | 0 |
| Du422.1 at dilution 80, measured at Month 6.5 | 0 | 0 | 0 |
| MW965.26 at dilution 50, measured at Month 6.5 | 8 | 7 | 0 |
| MW965.26 at dilution 80, measured at Month 6.5 | 8 | 7 | 0 |
Neutralizing antibodies against strains of HIV-1 were measured as a function of reductions in Tat-induced luciferase (Luc) reporter gene expression in TZMbl cells. A serum neutralization titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% (ID50 and ID80) relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only). The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped vaccine strains (Du422.1, Du172.17 and CH505TF) and a virus that exhibits a tier 1A neutralization phenotype (MW965.26). A titer was defined as the serum dilution that reduced relative luminescence units (RLUs) by 50% and 80% relative to the RLUs in virus control wells (cells + virus only) after subtraction of background RLU (cells only).
| titer | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|
| CH505TF at dilution 50, measured at Month 6.5 | 5 (5 to 5) | 5 (5 to 8.2) | 5 (5 to 5) |
| CH505TF at dilution 80, measured at Month 6.5 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| DU172.17 at dilution 50, measured at Month 6.5 | 5 (5 to 7.9) | 5 (5 to 5) | 5 (5 to 5) |
| DU172.17 at dilution 80, measured at Month 6.5 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| Du422.1 at dilution 50, measured at Month 6.5 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| Du422.1 at dilution 80, measured at Month 6.5 | 5 (5 to 5) | 5 (5 to 5) | 5 (5 to 5) |
| MW965.26 at dilution 50, measured at Month 6.5 | 2298.1 (898.4 to 3121.5) | 418.7 (102.2 to 1335.6) | 5 (5 to 5) |
| MW965.26 at dilution 80, measured at Month 6.5 | 757.6 (149 to 1145.8) | 104.5 (31.1 to 350.7) | 5 (5 to 5) |
Collected over All adverse events were collected for 30 after any receipt of study vaccination (up to 7 months). All serious adverse events (SAEs), medically attended adverse events (MAAEs), and adverse events of special interest (AESIs) were collected for twelve months following any receipt of study product (up to 18 months). Study vaccinations were given at study Day 0 (Month 0) for Part A (T1, T2, and C3) and at study Days 0 (Month 0), 84 (Month 3) and 168 (Month 6) for Part B (T4, T5, and C6).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A, Group 1: Vaccine | 0/5 (0%) | 0/5 (0%) | 1/5 (20%) |
| Part A, Group 2: Vaccine | 0/5 (0%) | 0/5 (0%) | 1/5 (20%) |
| Part A, Group 3: Placebo | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) |
| Part B, Group 4: Vaccine | 0/10 (0%) | 0/10 (0%) | 7/10 (70%) |
| Part B, Group 5: Vaccine | 1/10 (10%) | 1/10 (10%) | 3/10 (30%) |
| Part B, Group 6: Placebo | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) |
| Event | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Any Event in SOCInjury, poisoning and procedural complications | 0/5 | 0/5 | 0/2 | 0/10 | 1/10 | 0/2 |
| Stab woundInjury, poisoning and procedural complications | 0/5 | 0/5 | 0/2 | 0/10 | 1/10 | 0/2 |
| Event | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo |
|---|---|---|---|---|---|---|
| Any Event in SOCGastrointestinal disorders | 0/5 | 0/5 | 1/2 | 0/10 | 0/10 | 0/2 |
| Abdominal pain lowerGastrointestinal disorders | 0/5 | 0/5 | 1/2 | 0/10 | 0/10 | 0/2 |
| Any Event in SOCInfections and infestations | 0/5 | 1/5 | 0/2 | 5/10 | 1/10 | 0/2 |
| Urinary tract infectionInfections and infestations | 0/5 | 0/5 | 0/2 | 3/10 | 1/10 | 0/2 |
| Breast abscessInfections and infestations | 0/5 | 1/5 | 0/2 | 0/10 | 0/10 | 0/2 |
| Any Event in SOCInvestigations | 1/5 | 0/5 | 0/2 | 0/10 | 0/10 | 0/2 |
| Blood pressure increasedInvestigations | 1/5 | 0/5 | 0/2 | 0/10 | 0/10 | 0/2 |
| Any Event in SOCGeneral disorders | 0/5 | 0/5 | 0/2 | 1/10 | 0/10 | 0/2 |
| Influenza like illnessGeneral disorders | 0/5 | 0/5 | 0/2 | 1/10 | 0/10 | 0/2 |
| Body tineaInfections and infestations | 0/5 | 0/5 | 0/2 | 1/10 | 0/10 | 0/2 |
| Age, Continuous(years) | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Median | 23 (19 to 36) | 23 (18 to 32) | 24.5 (21 to 28) | 28 (19 to 35) | 28 (18 to 40) | 21.5 (20 to 23) | 25.5 (18 to 40) |
| Age, Customized(Participants) | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Less than 18 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 18-20 | 2 | 2 | 0 | 1 | 1 | 1 | 7 |
| 21-30 | 2 | 2 | 2 | 6 | 5 | 1 | 18 |
| 31-40 | 1 | 1 | 0 | 3 | 4 | 0 | 9 |
| 41-50 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Age Category : Above 50 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Female | 2 | 2 | 0 | 3 | 5 | 0 | 12 |
| Male | 3 | 3 | 2 | 7 | 5 | 2 | 22 |
| Ethnicity (NIH/OMB)(Participants) | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 5 | 5 | 2 | 10 | 10 | 2 | 34 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 5 | 5 | 2 | 10 | 10 | 2 | 34 |
| White | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo | Total |
|---|---|---|---|---|---|---|---|
| Black | 5 | 5 | 2 | 10 | 10 | 2 | 34 |
| White | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Indian | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Colored | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Part A, Group 1: Vaccine | Part A, Group 2: Vaccine | Part A, Group 3: Placebo | Part B, Group 4: Vaccine | Part B, Group 5: Vaccine | Part B, Group 6: Placebo | Total |
|---|---|---|---|---|---|---|---|
| South Africa | 5 | 5 | 2 | 10 | 10 | 2 | 34 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Nov 2021 to primary completion in Aug 2023, 20 months.
Results were first posted in Nov 2024, 1 year 3 months after primary completion.
Of 91 non-industry phase 1 interventional studies under HIV Infections, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 46. This study's 20 months is below that.
Counting every sponsor, half of 165 studies reached it within 19 months; a quarter within 7 and three quarters within 33.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: CH505TF
HIV Vaccine Trials Network