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 front subsequent intravaginal challenge with pathogenic SIVmac239 [Abel K. Compton L. Rourke T. Montefiori D. Lu D, RothaeUsler K. et al. Simian-hunian 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(50099-1 19. Miller CJ. McChesney MB, Lu X, Dailey PJ, Chutkowski C, Lu D, ct al. Rhesus macaques previously infected with simian/human immunodeficiency virus (HIV) are protected from vaginal challenge with pathogenic SIVmac239. J Virol 1997 7 1(3):1911-211. 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 lFN-gamma secreting cells on the day of mucosal SIVmac239 challenge, a smaller proportion of monkeys immunized with pMA SIIIV-89,0 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 liters 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 plwonid decreased the effectiveness of this live attenuated vaccine. (c) 2005 Elsevier Ltd. All rights reserved.