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Journal of Virology, April 1999, p. 3134-3146, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Protection of Macaques against Intrarectal Infection by a Combination Immunization Regimen with Recombinant Simian Immunodeficiency Virus SIVmne gp160 Vaccines

Patricia Polacino,1 Virginia Stallard,1,dagger David C. Montefiori,2 Charles R. Brown,3,Dagger Barbra A. Richardson,4 William R. Morton,1 Raoul E. Benveniste,5 and Shiu-Lok Hu1,6,*

Regional Primate Research Center1 and Department of Biostatistics,4 University of Washington, and Bristol-Myers Squibb Pharmaceutical Research Institute,6 Seattle, Washington; Duke University Medical Center, Durham, North Carolina2; and Henry M. Jackson Foundation, Rockville,3 and National Cancer Institute, Frederick,5 Maryland

Received 20 October 1998/Accepted 3 January 1999

We previously reported that immunization with recombinant simian immunodeficiency virus SIVmne envelope (gp160) vaccines protected macaques against intravenous challenge by the cloned homologous virus E11S but that this protection was only partially effective against the uncloned virus, SIVmne. In the present study, we examine the protective efficacy of this immunization regimen against infection by a mucosal route. We found that the same gp160-based vaccines were highly effective against intrarectal infection not only with the E11S clone but also with the uncloned SIVmne. Protection against mucosal infection is therefore achievable by parenteral immunization with recombinant envelope vaccines. Protection appears to correlate with high levels of SIV-specific antibodies and, in animals protected against the uncloned virus, the presence of serum-neutralizing activities. To understand the basis for the differential efficacies against the uncloned virus by the intravenous versus the intrarectal routes, we examined viral sequences recovered from the peripheral blood mononuclear cells of animals early after infection by both routes. We previously showed that the majority (85%) of the uncloned SIVmne challenge stock contained V1 sequences homologous to the molecular clone from which the vaccines were made (E11S type), with the remainder (15%) containing multiple conserved changes (the variant types). In contrast to intravenously infected animals, from which either E11S-type or the variant type V1 sequences could be recovered in significant proportions, animals infected intrarectally had predominantly E11S-type sequences. Preferential transmission or amplification of the E11S-type viruses may therefore account in part for the enhanced efficacy of the recombinant gp160 vaccines against the uncloned virus challenge by the intrarectal route compared with the intravenous route.

* Corresponding author. Present address: Department of Pharmaceutics and Regional Primate Research Center, Box 357331, University of Washington, Seattle, WA 98195. Phone: (206) 221-4939. Fax: (206) 543-3204. E-mail: hus{at}u.washington.edu.

dagger Present address: Sequim, Wash.

Dagger Present address: NIAID, Rockville, Md.

Journal of Virology, April 1999, p. 3134-3146, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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