Efficacy of a SHIV 89.6 proviral DNA vaccine against mucosal SIVmac239 challenge

Abstract

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-γ 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-γ 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.