Effects of Aging on Primary and Secondary Vaccine Responses (SLVP033)

Effects of Aging on Primary and Secondary Vaccine Responses in a 15-Year Longitudinal Cohort

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis A; Influenza; Healthy Adults; Typhoid
• Intervention / Treatment: Biological: Fluzone® quadrivalent; Biological: Fluzone High Dose; Biological: Fluad; Biological: Vaqta; Biological: Typhim Vi; Biological: Vivotif

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford LPCH Vaccine Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; 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.; Other Names: IIV4 inactivated influenza vaccine
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; 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.; Other Names: High Dose Trivalent, inactivated influenza vaccine (TIV)
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; 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.; Other Names: Adjuvanted Trivalent, inactivated influenza vaccine
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; Vaqta vaccine will be administered as a 1 mL dose, with a sterile, disposable syringe and needle by IM injection into the deltoid muscle.; Other Names: Inactivated Hepatitis A Vaccine
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; Vaqta vaccine will be administered as a 1 mL dose, with a sterile, disposable syringe and needle by IM injection into the deltoid muscle.; Other Names: Inactivated Hepatitis A Vaccine
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; 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.; Other Names: Typhoid Vi Polysaccharide Vaccine
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; 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.; Other Names: Typhoid Vaccine Live Oral Ty21a
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; 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.; Other Names: Typhoid Vi Polysaccharide Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hemagglutination inhibition assay (HAI) titers	HAI titers measured at Days 0 and 28 for influenza.	Day 0 to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Day 0 to Day 28 post-each immunization

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Cornelia Dekker, MD, Stanford School of Medicine, Dept. of Pediatrics; Principal Investigator: Scott Boyd, MD, PhD, Stanford School of Medicine, Dept. of Pathology

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2017
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: October 12, 2017
• First Submitted That Met QC Criteria: October 12, 2017
• First Posted (Actual): October 18, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• 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
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Enterobacteriaceae Infections; Salmonella Infections; Influenza, Human; Hepatitis A; Hepatitis; Typhoid Fever; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: 40216; R01AI130398-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: De-identified data will be loaded into ImmPort following completion of all data analysis
• IPD Sharing Access Criteria: De-identified data will be publicly available through ImmPort

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No