All ETDs from UAB

Advisory Committee Chair

Richard P Morrison

Advisory Committee Members

David E Briles

Edward W Hook Iii

Suzanne M Michalek

Roger G Rank

Document Type

Dissertation

Date of Award

2010

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Urogenital infection with Chlamydia trachomatis is the most common bacterial sexually transmit-ted disease with an estimated 90 million new infections occurring each year worldwide. In women infection with C. trachomatis can result in serious complications including ectopic pregnancy, pelvic inflammatory disease and tubal factor infertility. Despite very effective antimicrobial chemotherapy, control of the infection will likely require an effective vaccine. We have assessed the protective effect of an outer membrane based vaccine using a murine model of chlamydial genital tract infection. Female mice were vaccinated with C. muridarum major outer membrane protein (MOMP) plus the immunostimulatory adjuvants CpG-1826 and Montanide ISA 720, and then challenged vaginally with C. muridarum. Over the course of infection, vaccinated mice shed 2-3 log10 fewer IFU (inclusion forming units) than ovalbumin vaccinated (negative control) and naïve animals. MOMP vaccination also shortened the duration of the infection with 79% of animals resolving infection by day 21 versus 23% and 0% for ovalbumin vaccinated and naïve animals, respectively. To determine the relative contribution of T cells in vaccination-induced protection, mice were vaccinated, depleted of CD4+ or CD8+ T cells and then challenged vaginally with C. muridarum. Depletion of CD4+ T cells, but not CD8+ T cells, diminished vaccine-induced protection, with CD4+ T cell depleted mice shedding 2 to 4 log10 more IFU than CD8+ T cell depleted or non-depleted mice at all time points tested. The contribution of antibody in the vaccine-induced protective response was demonstrated by the lack of protective immunity in vaccinated antibody deficient mice; the infection course in vaccinated and non-vaccinated antibody deficient mice was indistinguishable. Furthering this observation, passively administered vaccine-induced anti-MOMP serum resulted in a 2 to 3 log10 IFU decrease in bacterial burden compared to non-treated mice. Thus, optimal protective immunity in this model of vaccine-induced protection depends on both CD4+ T cells and antibody.

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