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Journal of Virology, September 1999, p. 7430-7440, Vol. 73, No. 9
Basic Research Laboratory, National Cancer
Institute, Bethesda, Maryland 208921;
Advanced BioScience Laboratories, Inc., Kensington, Maryland
208952; California Regional Primate
Research Center, University of California at Davis, Davis, California
956163; and Wyeth-Ayerst Research,
Radnor, Pennsylvania 190874
Received 2 March 1999/Accepted 15 June 1999
Rhesus macaques were immunized with a combination vaccine regimen
consisting of adenovirus type 5 host range mutant-simian immunodeficiency virus envelope (Ad5hr-SIVenv) recombinant priming and
boosting with native SIV gp120. Upon intravaginal challenge with
SIVmac251, both persistently and transiently viremic animals were
observed (S. L. Buge, E. Richardson, S. Alipanah, P. Markham, S. Cheng, N. Kalyan, C. J. Miller, M. Lubeck, S. Udem, J. Eldridge, and M. Robert-Guroff, J. Virol. 71:8531-8541, 1997). Long-term follow-up of the persistently viremic immunized macaques, which displayed significantly reduced viral burdens during the first 18 weeks
postchallenge compared to controls, has now shown that one of four
became a slow progressor, clearing virus from plasma and remaining
asymptomatic with stable CD4 counts for 134 weeks postchallenge.
Reboosting of the transiently viremic macaques did not reactivate
latent virus. Rechallenge with two sequential SIVmac251 intravaginal
exposures again resulted in partial protection of one of two immunized
macaques, manifested by viral clearance and stable CD4 counts. No
single immune parameter was associated with partial protection.
Development of a strong antibody response capable of neutralizing a
primary SIVmac251 isolate together with SIV-specific cytotoxic T
lymphocytes were implicated, while CD8+ T-cell antiviral
activity and mucosal immune responses were not associated with delayed
disease progression. Our data show that even a third immunization with
the same Ad5hr-SIVenv recombinant can elicit significant immune
responses to the inserted gene product, suggesting that preexisting Ad
antibodies may not preclude effective immunization. Further, the
partial protection against a virulent, pathogenic SIV challenge
observed in two of six macaques immunized with a vaccine regimen based
solely on the viral envelope indicates that this vectored-vaccine
approach has promise and that multicomponent vaccines based in the same
system merit further investigation.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Factors Associated with Slow Disease Progression in
Macaques Immunized with an Adenovirus-Simian Immunodeficiency Virus
(SIV) Envelope Priming-gp120 Boosting Regimen and Challenged Vaginally
with SIVmac251
*
Corresponding author. Mailing address: Basic Research
Laboratory, National Cancer Institute, Building 41, Room D804, 41 Library Dr. MSC 5055, Bethesda, MD 20892-5055. Phone: (301) 496-2114. Fax: (301) 496-8394. E-mail: guroffm{at}exchange.nih.gov.
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