CompletedNCT05374317Updated Apr 7, 2026Results posted

Study of the Safety and Immunogenicity of Reduced Doses of the US Yellow Fever Vaccine

A Phase 4 interventional study of Yellow Fever Vaccine in Yellow Fever Vaccination Reaction, sponsored by US Army Medical Research Institute of Infectious Diseases. Completed at 1 site in United States. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-04-07.

Sponsored by US Army Medical Research Institute of Infectious Diseases · Phase 4, Interventional, and Health services research

From the registry’s dates

Registered 9 months after the study started (first participant enrolled Jun 2021, registered Mar 2022).

Phase: Phase 4
Study type: Interventional
Enrollment: 88
Allocation: Randomized
Ages: 18 Years to 50 Years
Sex: All

Study summary

This is an open-label, randomized, exploratory study to evaluate the human immune response to reduced subcutaneous (SQ) dosing of Yellow Fever vaccine compared to the standard FDA approved subcutaneous vaccination dose. The current dose of the US FDA licensed Yellow Fever vaccine is approximately 55,000 plaque-forming unit(s) (PFU) in 0.5 mL administered SQ. Using the licensed dosage as standard, investigators are evaluating reduced doses of 1/5th (0.10 mL) and 1/10th (0.05 mL) standard Yellow Fever vaccine (YF-VAX).

Read the detailed description

Up to 150 individuals will be screened in order to randomize 90 eligible individuals to one of three groups: Group 1- YF-VAX® standard dose 0.5 mL SQ = 30 subjects; Group 2-0.10 mL (1/5th) SQ = 30 subjects; Group 3-0.05 mL (1/10th) SQ = 30 subjects.

Conditions studied

Yellow Fever Vaccination Reaction

In context

Lead sponsor

This is the only study on the registry with US Army Medical Research Institute of Infectious Diseases as lead sponsor.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 50 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

Males and Females 18 to 50 years of age.
In good health, as determined by pertinent medical history, physical examination, vital signs, and clinical safety laboratory evaluations.
Female of child bearing potential: Has a negative pregnancy test and is willing to use a reliable form of contraception for the duration of the study after vaccination.
Negative human immunodeficiency virus (HIV) antibody screen, seronegative for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (following HIV and hepatitis testing, subjects will be provided with counseling and referral for health care if any test is positive).
Ability to comprehend and a willingness to sign an informed consent, which includes the Health Insurance Portability and Accountability Act (HIPAA) Authorization, and a separate consent form for HIV testing.
Be willing to comply with all follow-up visits, testing, adverse event (AE) reporting, and completion of diary card.

Exclusion criteria

Exclusion Criteria:

Receipt of any other investigational vaccine or investigational drug within 28 days prior to or after vaccination with YF-VAX® vaccine.
Have had any known flavivirus disease or receipt of any flavivirus vaccine, licensed or investigational at any time; in addition to any yellow fever vaccine, these include; Japanese Encephalitis (JE), St. Louis Encephalitis, Tick Borne Encephalitis (TBE), West Nile, Dengue, Zika virus
Anticipates receipt of any other vaccine within 28 days of YF-VAX®. Influenza vaccination will be permitted but not within 14 days of YF-VAX®.
Acute or chronic medical conditions, or medications that, in the Principal Investigator's (PI) opinion, would impair the subject's ability to respond to vaccination.
Hypersensitivity to any vaccine, eggs or egg products, or allergy to any component of the YF-VAX® (sorbitol, gelatin) or latex.
Corticosteroids ≥20 mg/day of prednisone for ≥ 2 weeks suppresses the immune system. Low-dose corticosteroid topical products and nasal sprays used sporadically (i.e. prn--according to circumstances) are permissible.
History of immunosuppression, by any cause--primary or acquired immunodeficiencies, transplantation, malignant neoplasm, lymphoma, leukemia, thymoma, myasthenia gravis, radiation, immunosuppressive drugs, including antimetabolites, tumor necrosis factor (TNF)-alpha inhibitors (etanercept), interleukin-1 (IL-1) blocking agents and other monoclonal antibodies targeting immune cells (e.g., rituximab, alemtuzumab, etc), etc.
Receipt of or anticipates receipt of/or donation of blood or blood products for 2 months after receipt of YF-VAX®. (Note: Blood banks require a minimum 2 week interval between the receipt of this FDA licensed vaccine and blood donations; however because of the blood collections in this study, an interval of 2 months is requested).
Female: Pregnant (or planning to become pregnant) or breastfeeding for the duration of the study after receipt of YF-VAX®.
Clinically significant abnormal laboratory tests (generally 2 times the upper limit of normal or as determined by the PI).

Study design

Phase: Phase 4
Primary purpose: Health services research
Allocation: Randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 88 participants (actual)

Study arms

Active comparator
Standard Dose (Group 1)
Yellow Fever vaccine standard dose, 0.5mL.
Biological: Yellow Fever Vaccine
Experimental
Fractional dose (Group 2)
Yellow Fever vaccine 1/5th standard dose, 0.1mL.
Biological: Yellow Fever Vaccine
Experimental
Fractional dose (Group 3)
Yellow Fever vaccine 1/10th standard dose, 0.05mL.
Biological: Yellow Fever Vaccine

Interventions

BiologicalYellow Fever Vaccine
Administered subcutaneously once.
Also known as: YF-VAX

What researchers measure

Primary outcomes

Adverse Events
Rate of Adverse Events of fractional doses vs standard dose of YF-VAX.
Time frame: Up to 28 days post vaccination
Neutralizing Antibody Response
For each group determine the PRNT50 neutralizing antibody response rate at the primary data point at post-vaccination day 28.
Time frame: The primary data point is day 28 post-vaccination.

Secondary outcomes

Viremia
Compare the rate of viremia by Reverse Transcription Polymerase Chain Reaction (RT-PCR) \[copies/mL\] of fractional doses vs standard dose.
Time frame: First 14 days following vaccination.

Results

Posted Apr 7, 2026

Limitations and caveats

This was a pilot study to establish proof of concept.

Participant flow

Participant flow — Overall Study
Milestone	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)
Started	29	30	29
Completed	23	25	24
Not completed	6	5	5

Outcome measures

PrimaryAdverse Events

Rate of Adverse Events of fractional doses vs standard dose of YF-VAX.

Time frame:: Up to 28 days post vaccination
Reported as:: Count of participants · Participants

Adverse Events
Participants	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)
Adverse Events	26	27	28

PrimaryNeutralizing Antibody Response

For each group determine the PRNT50 neutralizing antibody response rate at the primary data point at post-vaccination day 28.

Time frame:: The primary data point is day 28 post-vaccination.
Reported as:: Count of participants · Participants

Neutralizing Antibody Response
Participants	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)
Neutralizing Antibody Response	26	27	28

SecondaryViremia

Compare the rate of viremia by Reverse Transcription Polymerase Chain Reaction (RT-PCR) \[copies/mL\] of fractional doses vs standard dose.

Time frame:: First 14 days following vaccination.
Reported as:: Count of participants · Participants

Viremia
Participants	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)
Viremia	0	0	0

Statistical analysis

Standard Dose (Group 1) vs Fractional Dose (Group 2) vs Fractional Dose (Group 3) · ANOVA · p = 0.6173 · Mean difference (final values): 0.4937

Adverse events

Collected over Adverse Events collected Up to one year following vaccination.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Standard Dose (Group 1)	0/29 (0%)	1/29 (3.4%)	15/29 (51.7%)
Fractional Dose (Group 2)	0/30 (0%)	0/30 (0%)	11/30 (36.7%)
Fractional Dose (Group 3)	0/29 (0%)	0/29 (0%)	7/29 (24.1%)

Most frequent serious events

Most frequent serious events
Event	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)
Broken JawMusculoskeletal and connective tissue disorders	1/29	—	—

Most frequent other events

Most frequent other events
Event	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)
Injection Site PainGeneral disorders	8/29	4/30	2/29
Erythema at Injection SiteSkin and subcutaneous tissue disorders	7/29	2/30	0/29
HeadacheNervous system disorders	5/29	4/30	3/29
Bruise (vaccination site)Skin and subcutaneous tissue disorders	3/29	1/30	0/29
Induration (vaccination site)Skin and subcutaneous tissue disorders	3/29	0/30	0/29
Nasal CongestionRespiratory, thoracic and mediastinal disorders	0/29	0/30	2/29
Body AchesMusculoskeletal and connective tissue disorders	2/29	1/30	0/29
White Blood Cell DecreasedBlood and lymphatic system disorders	1/29	2/30	0/29
Neutrophil Count DecreasedBlood and lymphatic system disorders	1/29	2/30	0/29
Bruise: Blood Draw SiteBlood and lymphatic system disorders	0/29	2/30	0/29

Baseline characteristics

Analysis population included all subjects that signed consent \& were randomized to a study group. Two targeted populations were defined for this study as outlined below. 1. Safety will be analyzed for all subjects who receive an injection of vaccine regardless of adherence to the protocol (intent to treat). 2. Subjects who receive vaccine \& had titers drawn in compliance to protocol were included in the per protocol analysis set \& used for immunogenicity and exploratory analysis (per protocol).

Age, Categorical
Age, Categorical(Participants)	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)	Total
<=18 years	0	0	0	0
Between 18 and 65 years	29	30	29	88
>=65 years	0	0	0	0

Age, Continuous
Age, Continuous(Years)	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)	Total
Mean	34.2 ± 9.4	28.1 ± 7.1	35.2 ± 10.2	32.5 ± 9.4

Sex: Female, Male
Sex: Female, Male(Participants)	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)	Total
Female	13	13	12	38
Male	16	17	17	50

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)	Total
Hispanic or Latino	5	2	2	9
Not Hispanic or Latino	23	23	25	71
Unknown or Not Reported	1	5	2	8

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)	Total
Race — White	18	20	19	57
Race — Black/African American	3	1	3	7
Race — Asian	1	2	2	5
Race — Native Hawaiian/Pacific Islander	1	0	1	2
Race — American Indian/Alaskan Native	0	0	0	0
Race — Hispanic or Latino	5	2	2	9
Race — Others	1	5	2	8

Region of Enrollment
Region of Enrollment(participants)	Standard Dose (Group 1)	Fractional Dose (Group 2)	Fractional Dose (Group 3)	Total
United States	29	30	29	88

Study locations

1 site

United States Army Medical Research Institute of Infectious Diseases
Frederick, Maryland 21702, United States

References and documents

Publications

Vasconcelos PF, Monath TP. Yellow Fever Remains a Potential Threat to Public Health. Vector Borne Zoonotic Dis. 2016 Aug;16(8):566-7. doi: 10.1089/vbz.2016.2031. Epub 2016 Jul 11. PubMed 27400066 ↗
Monath TP, Woodall JP, Gubler DJ, Yuill TM, Mackenzie JS, Martins RM, Reiter P, Heymann DL. Yellow fever vaccine supply: a possible solution. Lancet. 2016 Apr 16;387(10028):1599-600. doi: 10.1016/S0140-6736(16)30195-7. Epub 2016 Apr 14. No abstract available. PubMed 27116054 ↗
Calisher CH, Woodall JP. Yellow Fever-More a Policy and Planning Problem than a Biological One. Emerg Infect Dis. 2016 Oct;22(10):1859-60. doi: 10.3201/eid2210.160875. Epub 2016 Oct 15. No abstract available. PubMed 27479749 ↗
Elachola H, Ditekemena J, Zhuo J, Gozzer E, Marchesini P, Rahman M, Sow S, Kattan RF, Memish ZA. Yellow fever outbreaks, vaccine shortages and the Hajj and Olympics: call for global vigilance. Lancet. 2016 Sep 17;388(10050):1155. doi: 10.1016/S0140-6736(16)31546-X. Epub 2016 Sep 5. No abstract available. PubMed 27609407 ↗
Roukens AH, Vossen AC, Bredenbeek PJ, van Dissel JT, Visser LG. Intradermally administered yellow fever vaccine at reduced dose induces a protective immune response: a randomized controlled non-inferiority trial. PLoS One. 2008 Apr 23;3(4):e1993. doi: 10.1371/journal.pone.0001993. PubMed 18431480 ↗
Slifka MK, Leung DY, Hammarlund E, Raue HP, Simpson EL, Tofte S, Baig-Lewis S, David G, Lynn H, Woolson R, Hata T, Milgrom H, Hanifin J. Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis. J Allergy Clin Immunol. 2014 Feb;133(2):439-47. doi: 10.1016/j.jaci.2013.10.037. Epub 2013 Dec 10. PubMed 24331381 ↗
Campi-Azevedo AC, de Almeida Estevam P, Coelho-Dos-Reis JG, Peruhype-Magalhaes V, Villela-Rezende G, Quaresma PF, Maia Mde L, Farias RH, Camacho LA, Freire Mda S, Galler R, Yamamura AM, Almeida LF, Lima SM, Nogueira RM, Silva Sa GR, Hokama DA, de Carvalho R, Freire RA, Filho EP, Leal Mda L, Homma A, Teixeira-Carvalho A, Martins RM, Martins-Filho OA. Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline. BMC Infect Dis. 2014 Jul 15;14:391. doi: 10.1186/1471-2334-14-391. PubMed 25022840 ↗
Wu JT, Peak CM, Leung GM, Lipsitch M. Fractional dosing of yellow fever vaccine to extend supply: a modelling study. Lancet. 2016 Dec 10;388(10062):2904-2911. doi: 10.1016/S0140-6736(16)31838-4. Epub 2016 Nov 10. PubMed 27837923 ↗
Visser LG, Roukens AH. Modelling a way out of yellow fever. Lancet. 2016 Dec 10;388(10062):2847-2848. doi: 10.1016/S0140-6736(16)31330-7. Epub 2016 Nov 10. No abstract available. PubMed 27837922 ↗
Casey RM, Harris JB, Ahuka-Mundeke S, Dixon MG, Kizito GM, Nsele PM, Umutesi G, Laven J, Kosoy O, Paluku G, Gueye AS, Hyde TB, Ewetola R, Sheria GKM, Muyembe-Tamfum JJ, Staples JE. Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report. N Engl J Med. 2019 Aug 1;381(5):444-454. doi: 10.1056/NEJMoa1710430. Epub 2018 Feb 14. PubMed 29443626 ↗
Martins RM, Maia Mde L, Farias RH, Camacho LA, Freire MS, Galler R, Yamamura AM, Almeida LF, Lima SM, Nogueira RM, Sa GR, Hokama DA, de Carvalho R, Freire RA, Pereira Filho E, Leal Mda L, Homma A. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study. Hum Vaccin Immunother. 2013 Apr;9(4):879-88. doi: 10.4161/hv.22982. Epub 2013 Jan 30. PubMed 23364472 ↗
Yellow fever vaccine: WHO position on the use of fractional doses - June 2017. Wkly Epidemiol Rec. 2017 Jun 23;92(25):345-50. No abstract available. English, French. PubMed 28643507 ↗
Roukens AHE, Visser LG. Fractional-dose yellow fever vaccination: an expert review. J Travel Med. 2019 Sep 2;26(6):taz024. doi: 10.1093/jtm/taz024. PubMed 30937437 ↗
Hepburn MJ, Kortepeter MG, Pittman PR, Boudreau EF, Mangiafico JA, Buck PA, Norris SL, Anderson EL. Neutralizing antibody response to booster vaccination with the 17d yellow fever vaccine. Vaccine. 2006 Apr 5;24(15):2843-9. doi: 10.1016/j.vaccine.2005.12.055. Epub 2006 Jan 18. PubMed 16494976 ↗
Hotez PJ, LaBeaud AD. Yellow Jack's Potential Return to the American South. N Engl J Med. 2023 Oct 19;389(16):1445-1447. doi: 10.1056/NEJMp2308420. Epub 2023 Oct 14. No abstract available. PubMed 37843124 ↗
Hansen CA, Staples JE, Barrett ADT. Fractional Dosing of Yellow Fever Live Attenuated 17D Vaccine: A Perspective. Infect Drug Resist. 2023 Nov 8;16:7141-7154. doi: 10.2147/IDR.S370013. eCollection 2023. PubMed 38023411 ↗

Study documents

Protocol and statistical analysis plan · Mar 14, 2023
Informed consent form · Sep 2, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 7, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05374317
Lead sponsor: US Army Medical Research Institute of Infectious Diseases
Responsible party: Sponsor
First posted: May 16, 2022
Start date: Jun 7, 2021
Primary completion: Nov 2, 2022
Completion: Nov 2, 2022
Results posted: Apr 7, 2026
Last update: Apr 7, 2026

Study contacts

Phillip R Pittman, M.D., M.P.H.

principal investigator · US Army Medical Research Institute of Infectious Diseases

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion