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Journal of Virology, March 2000, p. 2740-2751, Vol. 74, No. 6
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.
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
*
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.
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