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Influence of mismatch of env sequences on vaccine protection by live attenuated simian immunodeficiency virus

Manrique, J, Piatak, M, Lauer, W, Johnson, W, Mansfield, K, Lifson, J and Desrosiers, R (2013) Influence of mismatch of env sequences on vaccine protection by live attenuated simian immunodeficiency virus. Journal of Virology. pp. 7246-7254.


Vaccine/challenge experiments that utilize live attenuated strains of simian immunodeficiency virus (SIV) in monkeys may be useful for elucidating what is needed from a vaccine in order to achieve protective immunity. Derivatives of SIVmac239 and SIVmac239nef were constructed in which env sequences were replaced with those of the heterologous strain E543; these were then used in vaccine/challenge experiments. When challenge occurred at 22 weeks, 10 of 12 monkeys exhibited apparent sterilizing immunity despite a mismatch of Env sequences, compared to 12 of 12 monkeys with apparent sterilizing immunity when challenge virus was matched in its Env sequence. However, when challenge occurred at 6 weeks, 6 of 6 SIV239nef-immunized monkeys became superinfected by challenge virus mismatched in its Env sequence (SIV239/EnvE543). These results contrast markedly not only with the results of the week 22 challenge but also with the sterilizing immunity observed in 5 of 5 SIV239nef-immunized rhesus monkeys challenged at 5 weeks with SIV239, i.e., with no mismatch of Env sequences. We conclude from these studies that a mismatch of Env sequences in the challenge virus can have a dramatic effect on the extent of apparent sterilizing immunity when challenge occurs relatively early, 5 to 6 weeks after the nef-deleted SIV administration. However, by 22 weeks, mismatch of Env sequences has little or no influence on the degree of protection against challenge virus. Our findings suggest that anti-Env immune responses are a key component of the protective immunity elicited by live attenuated, nef-deleted SIV. 2013, American Society for Microbiology

Item Type: Article
Additional Information: pubid: 124 nvp_institute: NIBR contributor_address: (Manrique, Lauer, Johnson, Mansfield, Desrosiers) New England Primate Research Center, Harvard Medical School, Southborough, MA, United States (Piatak, Lifson) AIDS and Cancer Virus Program, SAIC Frederick, Inc., Frederick National Laboratory, Frederick, MD, United States (Manrique) Laboratory of Virology and Molecular Genetics, National University of Patagonia San Juan Bosco, Natural Science Faculty, Trelew National Council of Scientific and Technological Research, Chubut Province, Argentina (Johnson) Department of Biology, Boston College, Chestnut Hill, MA, United States (Mansfield) Novartis Institute for Biomedical Research, Cambridge, MA, United States
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12