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Journal of Virology, June 2009, p. 5388-5400, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02598-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Improved Survival in Rhesus Macaques Immunized with Modified Vaccinia Virus Ankara Recombinants Expressing Simian Immunodeficiency Virus Envelope Correlates with Reduction in Memory CD4+ T-Cell Loss and Higher Titers of Neutralizing Antibody{triangledown}

Ilnour Ourmanov, Takeo Kuwata,{dagger} Robert Goeken, Simoy Goldstein, Ranjani Iyengar, Alicia Buckler-White, Bernard Lafont, and Vanessa M. Hirsch*

Laboratory of Molecular Microbiology, NIAID, NIH, 4 Center Drive, Bethesda, Maryland 20892

Received 16 December 2008/ Accepted 11 March 2009

Previous studies demonstrated that immunization of macaques with simian immunodeficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvirus modified vaccinia virus Ankara (MVA) provided protection from high viremia and AIDS following challenge with a pathogenic strain of SIV. Although all animals became infected, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines compared with animals that received nonrecombinant MVA. Most importantly, the reduction in viremia resulted in a significant increase in median and cumulative survival. Continued analysis of these animals over the subsequent 9 years has shown that they maintain a survival advantage, although all but two of the macaques have progressed to AIDS. Importantly, improved survival correlated with preservation of memory CD4+ T cells in the peripheral blood. The greatest survival advantage was observed in macaques immunized with regimens containing SIV Env, and the titer of neutralizing antibodies to the challenge virus prior to or shortly following challenge correlated with preservation of CD4+ T cells. These data are consistent with a role for neutralizing antibodies in nonsterilizing protection from high viremia and associated memory CD4+ T-cell loss.

* Corresponding author. Mailing address: LMM, NIAID, NIH, Building 4, Room B1-41, 4 Center Drive, Bethesda, MD 20892. Phone: (301) 496-0559. Fax: (301) 480-3129. E-mail: vhirsch{at}niaid.nih.gov

{triangledown} Published ahead of print on 25 March 2009.

{dagger} Present address: Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto, Japan.

Journal of Virology, June 2009, p. 5388-5400, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.02598-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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