The induction of HIV Gag-specific CD8+ T cells in the spleen and gut-associated lymphoid tissue by parenteral or mucosal immunization with recombinant Listeria monocytogenes HIV Gag.
The induction of mucosal immunity is crucial in controlling viral replication during HIV infection. In this study we compare the ability of a recombinant Listeria monocytogenes that expresses and secretes the HIV Ag Gag to induce CD8(+) T cells against this Ag in the spleen, mesenteric lymph nodes, and Peyer's patches and the ability to provide effector Gag-specific CD8(+) T cells to the lamina propria after i.v., oral, or rectal administration of the vaccine. The levels of Ag-specific CD8(+)-activated T cells were measured ex vivo using intracellular cytokine staining for IFN-gamma and H-2K(d) Gag peptide tetramer staining. We found that all routes of immunization induced Gag-specific CD8(+) T cells in the spleen. After secondary infection, we observed substantial increases in splenic levels of CD8(+) T cells, and levels of Gag-specific cells were similar to those against listeriolysin O, the immunodominant Ag of L. monocytogenes. Both primary and secondary oral immunization resulted in abundant Gag-specific CD8(+)-activated T cells in the lamina propria that constituted approximately 35% of the CD8 compartment. However, significant levels of Gag and listeriolysin O-specific CD8(+) T cells were observed in mucosal lymphoid tissue only after two immunizations, perhaps because they had already entered the lamina propria compartment after a single immunization. In the context of HIV, a mucosally administered vaccine seems best calculated to prompt an immune response that is capable of preventing infection. The data presented in this report demonstrate that mucosally administered Listeria can prompt such a response and that booster doses can maintain this response.
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Christian
C
Peters
Xiaohui
X
Peng
Dennis
D
Douven
Zhen-Kun
ZK
Pan
Yvonne
Y
Paterson
D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D018988:Bacterial Translocation / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal / Q000235:genetics; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000382:microbiology / Q000821:virology; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D001428:Bacterial Vaccines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D014614:Vaccines, Synthetic