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Journal of Virology, March 2000, p. 2740-2751, Vol. 74, No. 6
0022-538X/00/$04.00+0

Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV

Ilnour Ourmanov,1 Charles R. Brown,1 Bernard Moss,2 Miles Carroll,2 Linda Wyatt,2 Liuobov Pletneva,1 Simoy Goldstein,1 David Venzon,3 and Vanessa M. Hirsch1,*

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852,1 and Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,2 and Biostatistics and Data Management Section, National Cancer Institute,3 Bethesda, Maryland 20892

Received 31 August 1999/Accepted 23 December 1999

Prior 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 levels of viremia and AIDS following challenge with a pathogenic strain of SIV (V. M. Hirsch et al., J. Virol. 70:3741-3752, 1996). This MVA-SIV recombinant expressed relatively low levels of the Gag-Pol portion of the vaccine. To optimize protection, second-generation recombinant MVAs that expressed high levels of either Gag-Pol (MVA-gag-pol) or Env (MVA-env), alone or in combination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was immunized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infected with uncloned pathogenic SIVsmE660. Although all animals became infected postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SIV recombinant vaccines as compared with animals that received nonrecombinant MVA (P = 0.0011 by repeated-measures analysis of variance). The differences in the degree of virus suppression achieved by the three MVA-SIV vaccines were not significant. Most importantly, the reduction in levels of viremia resulted in a significant increase in median (P < 0.05 by Student's t test) and cumulative (P = 0.010 by log rank test) survival. These results suggest that recombinant MVA has considerable potential as a vaccine vector for human AIDS.

* Corresponding author. Mailing address: NIAID Twinbrook II Facility, 12441 Parklawn Dr., Rockville, MD 20852. Phone: (301) 496-2976. Fax: (301) 480-2618. E-mail: vhirsch{at}nih.gov.

Journal of Virology, March 2000, p. 2740-2751, Vol. 74, No. 6
0022-538X/00/$04.00+0


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