Date of Award

Spring 2009

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Committee Director

Richard R. Drake

Committee Member

Yuping Deng

Committee Member

Julie A. Kerry

Committee Member

Noel K. Krishna

Abstract

The burden of influenza related infections is substantial, both in terms of illness, lives lost and economic impact on society. The degree of impact of influenza related infections is much higher in the elderly population where it is a leading cause of catastrophic disability; greatly affecting the quality of life of elderly persons above 65 years of age. Vaccination is the mainstay for control and prevention of influenza infections. There are two vaccine formulations that are licensed for use at present. The inactivated influenza vaccines (TIIV) which have been used for 60 years in all age groups and the new live attenuated influenza vaccine (LAIV) which is only recommended for use in individuals between 2-49 years of age. The mechanisms by which these two vaccines provide immunity in pre-vaccinated individuals have not been investigated in detail.

In our study we looked at the different immune correlates of vaccine responses and studied the mechanism by which these two vaccines provide immunity. We investigated age related changes in immune response to inactivated influenza vaccines between young and elderly. We also attempted to identify serum specific vaccine and age related immune senescence markers using mass spectrometric approach by using the MALDI-TOF MS technique.

We found contrasting immune responses induced by the two vaccines in different arms of the immune system. Our results showed that using antibody titer as the only standard to measure vaccine efficacy may lead to a bias towards parentarally administered vaccines. Our study showed significant age related differences in both humoral and cell mediate immune responses in the cohort immunized with inactive influenza vaccine. Elderly showed a decline in IFN-γ secretion as a result of age related decline in the function of influenza specific memory T cells. A positive correlation was observed between Th 1 T cell response and antibody response only in the elderly which suggested an important role of IFN-γ to antibody response in elderly. Our study did not find any relationship in baseline levels of IL-10, IL-6, TNF-α and 1L-1β cytokines affecting T cell or antibody response in the elderly which suggests that immune response to vaccination is not affected in the elderly due to a change in these cytokines with age. We also demonstrated that MALDI-TOF MS technique was not feasible in identifying vaccine response or immune senescence markers in healthy vaccinated individuals.

Comments

Dissertation Submitted to the Faculty of Eastern Virginia Medical School and Old Dominion University in Partial Fulfillment of the Requirement for the Degree of Doctor of Philosophy in Biomedical Sciences.

DOI

10.25777/vg7d-eq32

ISBN

9781109338447

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