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CompletedNCT03312699SLVP033Updated Dec 16, 2024

Effects of Aging on Primary and Secondary Vaccine Responses

A Phase 1 interventional study of Fluzone® quadrivalent and Fluzone High Dose in Influenza, Hepatitis A and Typhoid, sponsored by Stanford University. Completed at 1 site in United States. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-12-16.

Sponsored by Stanford University · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
54
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to use an existing, unique clinical cohort: the longitudinal cohort of younger (21-40 years) and elderly (>65 years) subjects whose yearly influenza vaccine responses have been studied extensively since 2007, to gain molecular and cellular mechanistic insights into the impaired vaccine responses in the elderly.

Read the detailed description

This is a phase I mechanistic study of sixty 21-40 and >65 year old adult volunteers who previously participated in vaccine studies with our program. All participation is by invitation only.

The volunteers will be enrolled into two groups. Group A: Up to 30 healthy adult volunteers age 21-40 who will be given seasonal quadrivalent inactivated influenza vaccine (IIV4) prior to flu season for each of 5 years. They will also be given an inactivated Hepatitis A vaccine in the spring of years 1 and 2. Each volunteer will complete a total of 4 visits for each immunization: Day 0 (pre-immunization), Day 6-8, Day 12-15, and Day 26-30 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

A subset of this group will be randomized to receive either a Typhoid Vi Polysaccharide Vaccine or Typhoid Vaccine Live Oral Ty21a vaccine in year 3. Each volunteer will complete a total of 4 visits for this immunization: Day 0 (pre-immunization), Day 6-8 post completion of injection or final oral dose, Day 12-15 and Day 26-30 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

Group B: Up to 30 healthy adult volunteers age 65 plus who will be randomized and given seasonal trivalent high dose inactivated influenza vaccine (IIV3) or trivalent adjuvanted trivalent inactivated influenza vaccine (Fluad) prior to flu season for each of 5 years. They will also be given an inactivated Hepatitis A vaccine in the spring of years 1 and 2 and aTyphoid Vi Polysaccharide Vaccine in year 3. Each volunteer will complete a total of 4 visits for each immunization: Day 0 (pre-immunization), Day 6-8, Day 12-15, and Day 26-30 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

A subset of subjects (with a target of 10 younger and 10 older subjects depending on health), will undergo bone marrow aspirates one or two years after typhoid vaccination.

02

Conditions studied

  • Influenza
  • Hepatitis A
  • Typhoid
  • Healthy Adults

Keywords

  • Inactivated, quadrivalent influenza vaccine
  • Inactivated Hepatitis A vaccine
  • Inactivated, trivalent high-dose influenza vaccine
  • Typhoid Vi Polysaccharide Vaccine
  • Typhoid Vaccine Live Oral Ty21a
  • Influenza Vaccine, Adjuvanted
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Provision of signed and dated informed consent form
  2. Stated willingness to comply with all study procedures and availability for the duration of the study.
  3. Prior participant in either the Ellison cohort or another Stanford vaccine study with archived samples.
  4. Male or female, aged 18-40 years or 65 years and older.
  5. In good general health as evidenced by medical history.

Exclusion criteria

Exclusion Criteria:

  1. Prior off-study vaccination with the current season influenza vaccine for influenza vaccinations.
  2. Allergy to egg or egg products
  3. Allergy to vaccine components, including thimerosal
  4. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
  5. Receipt of blood or blood products within the past 6 months of any study vaccination or planned receipt of blood products prior to completion of Day 28 post-immunization visit.
  6. Receipt of inactivated vaccine 14 days prior to study vaccination or planned vaccination prior to Day 28 after study vaccination.
  7. Receipt of live, attenuated vaccine within 60 days of study vaccination or planned vaccination prior to Day 28 after study vaccination.
  8. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or planned blood donation prior to Day 28 after study vaccination.
  9. Use of investigational agents within 30 days prior to enrollment or planned use of investigational agents prior to completion of all study visits.
  10. Need for allergy immunizations (that cannot be postponed) between Days 0 and 28 post-immunization.
  11. Pregnant or lactating woman for all but influenza vaccine. A woman who is pregnant or breastfeeding may be evaluated by the Protocol Director to determine if influenza vaccination would affect volunteer safety and may be included at the discretion of the investigator. Blood sample collection will be adjusted as necessary for volunteer safety (e.g. blood collection volume for a pregnant woman would follow the minimal risk guidelines of 50 ml in an 8 week period and collection may not occur more frequently than 2 times per week).
  12. Any condition, which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol.
04

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
54 participants (actual)

Study arms

  • Experimental
    Group A IIV4

    Group A: Up to 30 healthy volunteers 18-40 years old, will be given seasonal quadrivalent inactivated influenza vaccine (IIV4) Fluzone® Quadrivalent vaccine. Each volunteer will complete a total of 4 visits: Day 0 (pre-immunization), Day 6-8, Day 12-16, and Day 28+ 7 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

    Biological: Fluzone® quadrivalent

  • Experimental
    Group B High Dose IIV3

    Group B: Up to 15 healthy volunteers 65 plus years old, will be given seasonal high dose trivalent inactivated influenza vaccine (Fluzone High Dose) Fluzone® high dose vaccine. Each volunteer will complete a total of 4 visits: Day 0 (pre-immunization), Day 6-8, Day 12-16, and Day 28+ 7 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

    Biological: Fluzone High Dose

  • Experimental
    Group B Fluad

    Group B: Up to 15 healthy volunteers 65 plus years old, will be given seasonal adjuvanted trivalent inactivated influenza vaccine Fluad®. Each volunteer will complete a total of 4 visits: Day 0 (pre-immunization), Day 6-8, Day 12-16, and Day 28+ 7 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

    Biological: Fluad

  • Experimental
    Group A Hepatitis A (HepA)

    Group A: Up to 30 healthy volunteers 18-40 years old, will be given inactivated Hepatitis A vaccine Vaqta® in year 1 of the study and a booster 12 months post primary Vaqta vaccination. Each volunteer will complete a total of 4 visits per vaccination: Day 0 (pre-immunization), Day 6-8, Day 12-16, and Day 28+ 7 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

    Biological: Vaqta

  • Experimental
    Group B Hepatitis A

    Group B: Up to 30 healthy volunteers 65 plus years old, will be given inactivated Hepatitis A vaccine Vaqta® in year 1 of the study and a booster 12 months post primary Vaqta vaccination. Each volunteer will complete a total of 4 visits per vaccination: Day 0 (pre-immunization), Day 6-8, Day 12-16, and Day 28+ 7 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

    Biological: Vaqta

  • Experimental
    Group A Typhoid VI

    Group A: Up to 15 healthy volunteers 18-40 years old, will be randomized to either Typhoid Vi Polysaccharide Vaccine (Typhoid VI), Typhim Vi®, or Typhoid Vaccine Live Oral Ty21a, Vivotif®. This arm represents those randomized to Typhoid VI. Each volunteer will complete a total of 4 visits: Day 0 (pre-immunization), Day 6-8, Day 12-16, and Day 28+ 7 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

    Biological: Typhim Vi

  • Experimental
    Group A Oral Typhoid

    Group A: Up to 15 healthy volunteers 18-40 years old, will be randomized to either Typhoid Vi Polysaccharide Vaccine, Typhim Vi®, or Typhoid Vaccine Live Oral Ty21a, Vivotif® (Oral Typhoid). This arm represents those randomized to Oral Typhoid. Each volunteer will complete a total of 4 visits: Day 0 (pre-immunization), Day 6-8 (from date of last oral dose), Day 12-16, and Day 28+ 7 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

    Biological: Vivotif

  • Experimental
    Group B Typhoid VI

    Group B: Up to 30 healthy volunteers 65 plud years old, will be given Typhoid Vi Polysaccharide Vaccine (Typhoid VI), Typhim Vi® vaccine. Each volunteer will complete a total of 4 visits: Day 0 (pre-immunization), Day 6-8, Day 12-16, and Day 28+ 7 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

    Biological: Typhim Vi

Interventions

  • BiologicalFluzone® quadrivalent

    IIV4 vaccine will be administered as a 0.5 mL dose, with a sterile, disposable syringe and needle by intramuscular (IM) injection into the deltoid muscle.

    Also known as: IIV4 inactivated influenza vaccine

  • BiologicalFluzone High Dose

    High Dose IIV3 vaccine will be administered as a 0.5 mL dose, with a sterile, disposable syringe and needle by IM injection into the deltoid muscle.

    Also known as: High Dose Trivalent, inactivated influenza vaccine (TIV)

  • BiologicalFluad

    Fluad vaccine will be administered as a 0.5 mL dose, with a sterile, disposable syringe and needle by IM injection into the deltoid muscle.

    Also known as: Adjuvanted Trivalent, inactivated influenza vaccine

  • BiologicalVaqta

    Vaqta vaccine will be administered as a 1 mL dose, with a sterile, disposable syringe and needle by IM injection into the deltoid muscle.

    Also known as: Inactivated Hepatitis A Vaccine

  • BiologicalTyphim Vi

    Typhim Vi vaccine will be administered as a 0.5 mL dose, with a sterile, disposable syringe and needle by IM injection into the deltoid muscle.

    Also known as: Typhoid Vi Polysaccharide Vaccine

  • BiologicalVivotif

    One capsule is to be swallowed approximately 1 hour before a meal with a cold or luke-warm \[temperature not to exceed body temperature, e.g., 37 °C (98.6 °F)\] drink on alternate days, e.g., days 1, 3, 5 and 7.

    Also known as: Typhoid Vaccine Live Oral Ty21a

05

What researchers measure

Primary outcomes

  1. hemagglutination inhibition assay (HAI) titers

    HAI titers measured at Days 0 and 28 for influenza.

    Time frame: Day 0 to Day 28

Secondary outcomes

  1. related AEs occurring during the 28 days post vaccination

    related AEs occurring during the 28 days post vaccination for each of the vaccination types (Influenza, Hepatitis A, Typhoid)

    Time frame: Day 0 to Day 28 post-each immunization

06

Study locations

1 site
  • Stanford LPCH Vaccine Program
    Stanford, California 94305, United States
07

References and documents

Study documents

  • Informed consent form · Feb 16, 2022

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

Individual participant data

Plan to share: Yes — The NIH Human Immunology Project Consortium (HIPC) data repositories (ImmPORT) may store the results of the research assays results. Genetic data that is developed in this study may be made available to other researchers through the National Center for Biotechnology Information (NCBI) databases. Results from research assays will be labeled with a unique identification code and the volunteer identity (except for age) will not be disclosed.

08

Registry details

Key details

Study ID
NCT03312699
Lead sponsor
Stanford University
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party
Philip Grant (Assistant Professor of Medicine (Infectious Diseases), Stanford University) — Principal investigator
First posted
Oct 18, 2017
Start date
Sep 19, 2017
Primary completion
Dec 31, 2023
Completion
Dec 31, 2023
Last update
Dec 16, 2024

Study contacts

Scott Boyd, MD, PhD
principal investigator · Stanford School of Medicine, Dept. of Pathology
Cornelia Dekker, MD
principal investigator · Stanford School of Medicine, Dept. of Pediatrics

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2024. You cannot join it, but the record below documents what was studied.

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