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Journal of Virology, October 1999, p. 8201-8215, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Role of Immune Responses against the Envelope and the Core Antigens of Simian Immunodeficiency Virus SIVmne in Protection against Homologous Cloned and Uncloned Virus Challenge in Macaques

Patricia S. Polacino,1 Virginia Stallard,1,dagger James E. Klaniecki,2,Dagger Sridhar Pennathur,2,§ David C. Montefiori,3 Alphonse J. Langlois,3 Barbra A. Richardson,4 William R. Morton,1 Raoul E. Benveniste,5 and Shiu-Lok Hu1,2,*

Regional Primate Research Center1 and Department of Biostatistics,4 University of Washington, and Bristol-Myers Squibb Pharmaceutical Research Institute,2 Seattle, Washington; Duke University Medical Center, Durham, North Carolina3; and National Cancer Institute, Frederick, Maryland5

Received 15 March 1999/Accepted 2 July 1999

We previously showed that envelope (gp160)-based vaccines, used in a live recombinant virus priming and subunit protein boosting regimen, protected macaques against intravenous and intrarectal challenges with the homologous simian immunodeficiency virus SIVmne clone E11S. However, the breadth of protection appears to be limited, since the vaccines were only partially effective against intravenous challenge by the uncloned SIVmne. To examine factors that could affect the breadth and the efficacy of this immunization approach, we studied (i) the effect of priming by recombinant vaccinia virus; (ii) the role of surface antigen gp130; and (iii) the role of core antigens (Gag and Pol) in eliciting protective immunity. Results indicate that (i) priming with recombinant vaccinia virus was more effective than subunit antigen in eliciting protective responses; (ii) while both gp130 and gp160 elicited similar levels of SIV-specific antibodies, gp130 was not as effective as gp160 in protection, indicating a possible role for the transmembrane protein in presenting functionally important epitopes; and (iii) although animals immunized with core antigens failed to generate any neutralizing antibody and were infected upon challenge, their virus load was 50- to 100-fold lower than that of the controls, suggesting the importance of cellular immunity or other core-specific immune responses in controlling acute infection. Complete protection against intravenous infection by the pathogenic uncloned SIVmne was achieved by immunization with both the envelope and the core antigens. These results indicate that immune responses to both antigens may contribute to protection and thus argue for the inclusion of multiple antigens in recombinant vaccine designs.

* Corresponding author. Present address: Regional Primate Research Center, University of Washington, 3000 Western Ave., Seattle, WA 98121. Phone: (206) 616-9764. Fax: (206) 956-0573. E-mail: hus{at}u.washington.edu.

dagger Present address: Sequim, Wash.

Dagger Present address: Seattle, Wash.

§ Present address: Aviron, Mountain View, Calif.

Journal of Virology, October 1999, p. 8201-8215, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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