Influenza Vaccine Responses as a Means of Assessing Immune Competence in Chimeric Kidney/Stem Cell Transplant Recipients

Influenza infection in solid organ transplant recipients is associated with increased
morbidity and mortality compared to non-transplanted controls, due in part to the effects of
immunosuppression which is necessary to prevent rejection of the transplanted organ. Annual
influenza vaccination is the best way to prevent influenza infection and current CDC, AST
Infectious Diseases Community of Practice and American Society for Blood and Marrow
Transplantation guidelines recommend annual influenza vaccination to all transplant
recipients. However, transplant patients are less likely to produce antibodies when
vaccinated and when they do, the peak and duration of antibody responses are reduced
compared to healthy controls. There are considerable differences in the magnitude of these
responses, reflecting variability in individual responses to the influenza vaccine and to
the immunosuppression regimen.

Over the past several years, the investigators have conducted a Phase 2 clinical trial of
combined kidney and stem cell transplantation that has been successful in achieving
transplantation tolerance in a significant number of recipients. A central tenant for
transplantation tolerance is a selective loss of immune reactivity to the allograft while
preserving immune responses to all other antigens. The investigators hypothesize that
chimeric kidney transplant recipients off of immunosuppression will have post vaccine immune
responses that are comparable to age and gender matched healthy controls. The proposed
studies aim to assess the immune competence in these fully chimeric tolerant recipients, by
quantifying their T and B cell responses to the 2015-2016 inactivated influenza vaccine,
quadrivalent (IIV4), standard dose and by testing whether the responding T and B cells arise
from memory cells of recipient origin.

These studies will allow the investigators to quantify the influenza -specific cellular,
humoral, and molecular responses to IIV4 in tolerant vs. matched controls. On days 0 and 30
days post -IIV4, the flu-specific B cell and neutralizing antibody responses, and the
flu-specific IFN-gamma T cell response will be quantified. Additionally, the investigators
will perform genome-wide gene expression profiling on isolated PBMC on days 0 and 30
post-IIV4 to characterize the blood response at the transcriptome level.

Inclusion Criteria:

- Adults who have received either a combined kidney/stem cell transplant and have
achieved chimerism or post-transplant recipients who are maintained on standard
immunosuppressive therapy. Additionally, healthy controls of either gender ≥ 18 years
of age will also be recruited.

- Subjects must be willing and able to receive the IIV4 and provide blood samples at
research visits.

- Subjects must be willing and able to read, understand, and be capable of giving
informed consent for prospective enrollment.

Exclusion Criteria

- Subjects less than 18 years of age.

- Any condition that, in the opinion of the attending physician, would place the
patient at undue risk by participating. Specific conditions include but are not
limited to anemia prohibitive of phlebotomy, coagulopathy or inability to receive the
IIV4.