title: Influence of mismatch of Env sequences on vaccine protection by live attenuated simian immunodeficiency virus.
abstract: 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 SIVmac239Δnef 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 SIV239Δnef-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 SIV239Δnef-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.
authors: New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA.
authors: Julieta
authors: J
authors: Manrique
authors: Michael
authors: M
authors: Piatak
authors: William
authors: W
authors: Lauer
authors: Welkin
authors: W
authors: Johnson
authors: Keith
authors: K
authors: Mansfield
authors: Jeffrey
authors: J
authors: Lifson
authors: Ronald
authors: R
authors: Desrosiers
mesh_terms: D000818:Animals; D001483:Base Sequence; D058501:Enzyme-Linked Immunospot Assay; D015686:Gene Products, env / Q000235:genetics* / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*; D019562:Viral Load; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology
chemical_list: D015686:Gene Products, env; D014765:Viral Vaccines; D007371:Interferon-gamma
references: J Virol. 1999 Jan;73(1):436-43
references: 9847349
references: Virology. 2005 Mar 15;333(2):226-38
references: 15721357
references: Nature. 2012 Jan 04;482(7383):89-93
references: 22217938
references: AIDS Res Hum Retroviruses. 1990 Nov;6(11):1221-31
references: 2078405
references: J Virol. 1999 Jun;73(6):4952-61
references: 10233957
references: J Immunol. 2010 Jan 1;184(1):476-87
references: 19949078
references: Science. 1990 Jun 1;248(4959):1109-12
references: 2160735
references: J Virol. 2000 Mar;74(6):2740-51
references: 10684290
references: AIDS Res Hum Retroviruses. 1994 Feb;10(2):213-20
references: 8198874
references: J Med Primatol. 2005 Oct;34(5-6):303-12
references: 16128925
references: Vaccine. 2009 Aug 6;27(36):4990-5000
references: 19531389
references: PLoS Biol. 2010 Aug 24;8(8):
references: 20808775
references: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4144-9
references: 12644702
references: Nat Med. 2012 Nov;18(11):1673-81
references: 22961108
references: J Virol. 1999 Oct;73(10):8356-63
references: 10482586
references: J Exp Med. 2006 Nov 27;203(12):2661-72
references: 17116733
references: Curr HIV Res. 2010 Dec;8(8):596-601
references: 21054252
references: J Virol. 2010 Sep;84(18):9190-9
references: 20592091
references: J Virol. 1997 Jul;71(7):5069-79
references: 9188572
references: J Virol. 1997 Feb;71(2):1608-20
references: 8995688
references: Nat Med. 1999 Jul;5(7):723-5
references: 10395309
references: J Virol. 1997 Oct;71(10):7895-902
references: 9311879
references: Cell. 1991 May 17;65(4):651-62
references: 2032289
references: J Virol. 1993 Jul;67(7):4104-13
references: 8510218
references: J Virol. 2009 Jun;83(11):5388-400
references: 19321617
references: J Virol. 1998 Sep;72(9):7501-9
references: 9696847
references: J Virol. 2010 Mar;84(6):2996-3003
references: 20042509
references: Science. 1992 Dec 18;258(5090):1938-41
references: 1470917
references: PLoS Pathog. 2007 Nov;3(11):e177
references: 18020705