Listeria monocytogenes as a Biologic Vaccine Vector Against Feline Immunodeficiency Virus

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Title: Listeria monocytogenes as a Biologic Vaccine Vector Against Feline Immunodeficiency Virus
Author: Stevens, Rosemary
Advisors: Gregg Dean, Committee Chair
Frederick Fuller, Committee Member
Edward Havell, Committee Member
Mary Jo Burkhard, Committee Member
Abstract: Using the feline immunodeficiency virus (FIV) model of human immunodeficiency virus (HIV) we evaluated a recombinant L. monocytogenes vaccine in an FIV challenge system. In the first study, five cats were immunized with recombinant L. monocytogenes (LMgag/pND14-Lc-env). Control cats were either sham immunized or immunized with wild-type L. monocytogenes (10403S, LM-wt). One year post vaginal FIV challenge, all animals were sacrificed and tissues were harvested. Provirus was not detected by real-time PCR in any tissue evaluated from LMgag/pND14-Lc-env immunized cats. These cats maintained normal CD4:CD8 ratios in mesenteric lymph nodes while control cats had inverted ratios. While single, low-dose immunization with LMgag/pND14-Lc-env did not prevent FIV infection; it did reduce viral loads and enabled immunized cats to control viral replication. The second study addressed two questions, 1) vaccine efficacy in the face of pre-existing vector immunity, and 2) peripheral blood as an indicator of vaccine-induced immune responses. We examined the immunogenicity of LMgag/pND14-Lc-env in cats previously infected with LM-wt. Eight subcutaneously infected cats were divided into two groups of four. One group received 5x106 cfu LM-wt orally followed two months later with 1x108 cfu oral LMgag/pND14-Lc-env. The other group received 1x108 cfu oral LMgag/pND14-Lc-env. After a single oral dose of LMgag/pND14-Lc-env, cats with existing anti-L. monocytogenes immune responses developed anti-FIV Gag IgA titers in vaginal secretions, saliva, and feces. Similarly, FIV Gag and Env specific IFN-g ELISPOT responses were measurable in spleen and lymph node, but at a statistically higher frequency in cats exposed to a single subcutaneous dose of LM-wt compared to cats with two previous exposures. We also addressed the question of appropriateness of peripheral blood as a measurement of systemic and mucosal vaccine-specific immune responses. Our results show that there is no relationship between response measured in PBMC and that observed in splenic or lamina propria lymphocytes. Together, these studies show the ability of the oral vaccine LMgag/pND14-Lc-env to control viral load upon vaginal challenge and to generate anti-FIV antibodies and CD8 T cell response in the face of existing anti-listerial immunity.
Date: 2005-07-20
Degree: PhD
Discipline: Immunology

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