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

This is a phase IV 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.

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.