Mucosal DNA vaccination with highly attenuated Shigella is superior to attenuated Salmonella and comparable to intramuscular DNA vaccination for T cells against HIV.
An immunization strategy using attenuated bacteria to deliver DNA vaccine plasmids to mucosal sites may induce protective T cell responses against sexual HIV transmission. In a murine intranasal (i.n.) immunization model, we demonstrate that transiently persistent Deltaasd Shigella flexneri strain 15D harboring DNA vaccines induces HIV- and SIV-specific gamma interferon (IFN-gamma) producing CD8+ T cells among splenocytes more efficiently than either a longer persisting DeltaaroD Salmonella typhimurium strain SL7207 or transiently persistent S. typhi strain Ty21a harboring DNA vaccines. Also, the frequency of antigen-specific gamma interferon (IFN-gamma) producing cells induced by Shigella 15D harboring a DNA vaccine were comparable to that induced by intramuscular (i.m.) immunization with purified DNA vaccine. Moreover, the magnitude of mucosal and systemic antigen-specific IgA and IgG responses after immunization were dependent upon the route (i.m. vs. i.n.) of inoculation, with i.n. Shigella 15D DNA vaccines generating higher levels of HIV-specific IgA in vaginal washings than i.m. purified DNA vaccine. Deltaasd S. flexneri is a promising vector for mucosal DNA vaccine immunization against HIV.
Vecino
William H
WH
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Morin
Paul M
PM
Agha
Rabia
R
Jacobs
William R
WR
Fennelly
Glenn J
GJ
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology; D006678:HIV / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa; D012475:Salmonella / Q000276:immunology*; D012760:Shigella / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D015693:Gene Products, nef; D015699:HIV Envelope Protein gp120; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D054311:nef Gene Products, Human Immunodeficiency Virus