Efficacy of a SHIV 89.6 proviral DNA vaccine against mucosal SIVmac239 challenge.
Sixty percent of rhesus macaques infected with virulence attenuated virus SHIV 89.6 are protected from subsequent intravaginal challenge with pathogenic SIVmac239 [Abel K, Compton L, Rourke T, Montefiori D, Lu D, Rothaeusler K, et al. Simian-human immunodeficiency virus SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239 is independent of the route of immunization and is associated with a combination of cytotoxic T-lymphocyte and alpha interferon responses. J Virol 2003;77(5):3099-118; Miller CJ, McChesney MB, Lu X, Dailey PJ, Chutkowski C, Lu D, et al. Rhesus macaques previously infected with simian/human immunodeficiency virus (HIV) are protected from vaginal challenge with pathogenic SIVmac239. J Virol 1997;71(3):1911-21]. Previously, we have shown that inoculation with a proviral plasmid encoding SHIV 89.6 (pMA SHIV-89.6) results in systemic infection that is delayed compared to SHIV 89.6 virus inoculation [Busch M, Lu D, Fritts L, Lifson JD, Miller CJ. Comparison of virology and immunology in SHIV 89.6 proviral DNA and virus-inoculated rhesus macaques. J Med Primatol 2003;32(4-5):240-6]. We now report that, although monkeys inoculated with pMA SHIV-89.6 or SHIV 89.6 virus had similar plasma anti-SIV binding antibody titers and number of anti-SIV IFN-gamma secreting cells on the day of mucosal SIVmac239 challenge, a smaller proportion of monkeys immunized with pMA SHIV-89.6 were protected from vaginal SIVmac239 challenge compared to monkeys immunized using SHIV 89.6 virus. Protected DNA immunized monkeys had stronger anti-SIV IFN-gamma ELISPOT responses in the acute stage post-challenge than unprotected monkeys. Plasma anti-SIV binding antibody titers and PBMC cytokine responses in the acute stages post-challenge were similar in DNA vaccinated-protected and DNA vaccinated-unprotected monkeys. These results suggest that the delay in systemic infection resulting from delivery of SHIV 89.6 as a plasmid decreased the effectiveness of this live attenuated vaccine.
Busch
Marc
M
California National Primate Research Center, University California-Davis, County Road 98, Hutchison Drive, Davis, CA 95616, USA.
Abel
Kristina
K
Li
Jun
J
Piatak
Michael
M
Lifson
Jeffrey D
JD
Miller
Christopher J
CJ
D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D016207:Cytokines / Q000032:analysis; D004279:DNA, Viral / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta; D008297:Male; D011533:Proviruses / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000276:immunology*; D019562:Viral Load
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D016207:Cytokines; D004279:DNA, Viral; D012367:RNA, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma