Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) Gag-Pol and/or Env in macaques challenged with pathogenic SIV

Prior studies demonstrated that immunization of macaques with simian immuno deficiency virus (SIV) Gag-Pol and Env recombinants of the attenuated poxvi rus modified vaccinia virus Ankara (MVA) provided protection from high leve ls 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 recombina nt expressed relatively low levels of the Gag-Pol portion of the vaccine. T o optimize protection, second-generation recombinant MVAs that expressed hi gh levels of either Gag-Pol (MVA-gag-pol) or Env (MVA-env), alone or in com bination (MVA-gag-pol-env), were generated. A cohort of 24 macaques was imm unized with recombinant or nonrecombinant MVA (four groups of six animals) and was challenged with 50 times the dose at which 50% of macaques are infe cted with uncloned pathogenic SIVsmE660. Although all animals became infect ed postchallenge, plasma viremia was significantly reduced in animals that received the MVA-SN recombinant vaccines as compared with animals that rece ived nonrecombinant MVA (P = 0.0011 by repeated-measures analysis of varian ce). The differences in the degree of virus suppression achieved by the thr ee MVA-SIV vaccines were not significant. Most importantly, the reduction i n 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.