Standard-dose Versus High-dose Flu Vaccine in Solid Organ Transplant.

A potential strategy to enhance immune responses to influenza vaccine in this patient
population could be to use different strengths of TIV. One of the pathways that can improve
the immunogenicity of inactivated vaccines is to increase the dose of influenza antigens
contained in the vaccine. Studies have demonstrated that increasing the dose of the influenza
virus hemagglutinin for each of the commonly encountered viral strains beyond the
conventional dose of 15 microgram for each strain is associated with dose-dependent increase
in serum antibody titers.

Influenza TIV is commercially available in two different strengths, Fluzone as well as
Fluzone High-Dose, and it is valuable because of variable immunogenic potency of different
strengths. Fluzone is approved for use in persons 6 months of age and older. High-dose
Fluzone is approved for use in persons 65 years of age and older.

The purpose of this exploratory study is to assess the safety, tolerability, and
immunogenicity of these two commercially available different strengths of TIV in solid organ
transplant recipients (kidney, heart and lung) in the period after 30 days after transplant
procedure. We will evaluate the safety, tolerability (reactogenicity) and immunogenicity of
two different strengths of commercially available TIV in a single center, cluster
randomization, investigator blinded, study by enrolling patients in the post-transplant
clinic at Inova Fairfax Hospital from: August 1, 2013 - March 31, 2014; and August 1, 2014 to
March 31, 2015.

Study protocol will remain active till December 31, 2016. All bio-specimens will be stored
till December 31, 2016.

Inclusion Criteria:

1. All adults age ≥18 years of age following solid organ transplants (kidney, heart and
lung) of all races and gender unless as specified in the exclusion criteria.

2. At least 30 days after organ transplantation of kidney, heart, or lung.

3. In good health as determined by a) medical history, b) physical examinations, c)
clinical judgment of the investigator team.

4. Informed consent will be obtained from all the subjects before enrollment into the
study, after the nature of the study has been fully explained to the satisfaction of
the participant.

5. Non-English speaking persons will be included ONLY if consent can be obtained with the
help of the translator or interpreter.

Exclusion Criteria:

1. Less than 30 days after transplantation procedure.

2. Post operative complications of any type.

3. Transplant organ dysfunction and/or under evaluation for possible infection.

4. Recent acute transplant rejection and treatment for rejection for the past 30 days.

5. Receiving another investigational drug or biologic for transplant.

6. Previous history of allergic reaction to influenza vaccine, chicken egg or other
unknown allergic reactions to flu vaccine or other vaccines.

7. Acute ongoing respiratory illness.

8. Bleeding diathesis or on anticoagulation therapy.

9. Major surgery (pre-arranged) planned during the study period.

10. Any condition that may preclude the participant from completion of study related
activities; such as planned travel, or out of the state of residence and not able to
return for follow-up visits or relocation of residence.

11. Females of reproductive age unless proven to be urine HCG negative at the time of
participation.

12. Recent opportunistic infection, such as CMV, EBV, BK viral reactivation, or any other
documented or laboratory confirmed opportunistic infection or on treatment for
confirmed infection.

13. Vulnerable subjects such as aged less than 18 years, pregnant women, nursing home
residents or other institutionalized persons, students, employees, prisoners, and
persons who may not be able to make independent decisions or is considered to have a
cognitive impairment, or non-English speaking in the absence of a reliable interpreter
or translator.