title: Oral immunization with recombinant listeria monocytogenes controls virus load after vaginal challenge with feline immunodeficiency virus.
abstract: Recombinant Listeria monocytogenes has many attractive characteristics as a vaccine vector against human immunodeficiency virus (HIV). Wild-type and attenuated Listeria strains expressing HIV Gag have been shown to induce long-lived mucosal and systemic T-cell responses in mice. Using the feline immunodeficiency virus (FIV) model of HIV we evaluated recombinant L. monocytogenes in a challenge system. Five cats were immunized with recombinant L. monocytogenes that expresses the FIV Gag and delivers an FIV Env-expressing DNA vaccine (LMgag/pND14-Lc-env). Control cats were either sham immunized or immunized with wild-type L. monocytogenes (LM-wt). At 1 year after vaginal challenge, provirus could not be detected in any of the nine tissues evaluated from cats immunized with the recombinant bacteria but was detected in at least one tissue in 8 of 10 control animals. Virus was isolated from bone marrow of four of five LMgag/pND14-Lc-env-immunized cats by use of a stringent coculture system but required CD8(+) T-cell depletion, indicating CD8(+) T-cell suppression of virus replication. Control animals had an inverted CD4:CD8 ratio in mesenteric lymph node and were depleted of both CD4(+) and CD8(+) intestinal epithelial T cells, while LMgag/pND14-Lc-env-immunized animals showed no such abnormalities. Vaginal FIV-specific immunoglobulin A was present at high titer in three LMgag/pND14-Lc-env-immunized cats before challenge and in all five at 1 year postchallenge. This study demonstrates that recombinant L. monocytogenes conferred some control of viral load after vaginal challenge with FIV.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Stevens
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Howard
authors.forename: Sushila
authors.initials: S
authors.lastname: Nordone
authors.forename: MaryJo
authors.initials: M
authors.lastname: Burkhard
authors.forename: Gregg A
authors.initials: GA
authors.lastname: Dean
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002415:Cats; D016181:Feline Acquired Immunodeficiency Syndrome / Q000517:prevention & control* / Q000821:virology; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D016089:Immunodeficiency Virus, Feline / Q000302:isolation & purification*; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology; D008089:Listeria monocytogenes / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology; D008212:Lymphocyte Depletion; D011533:Proviruses / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000276:immunology*; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015683:Gene Products, gag; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D014765:Viral Vaccines