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Journal of Virology, January 1999, p. 618-630, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Limited Breadth of the Protective Immunity Elicited by Simian Immunodeficiency Virus SIVmne gp160 Vaccines in a Combination Immunization Regimen

Patricia Polacino,1 Virginia Stallard,1,dagger James E. Klaniecki,2,Dagger David C. Montefiori,3 Alphonse J. Langlois,3 Barbra A. Richardson,4 Julie Overbaugh,5 William R. Morton,1 Raoul E. Benveniste,6 and Shiu-Lok Hu1,2,*

Regional Primate Research Center,1 Department of Biostatistics,4 and Department of Microbiology,5 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, Maryland6

Received 23 June 1998/Accepted 29 September 1998

We previously reported that immunization with recombinant simian immunodeficiency virus SIVmne envelope (gp160) vaccines protected macaques against an intravenous challenge by the cloned homologous virus, E11S. In this study, we confirmed this observation and found that the vaccines were effective not only against virus grown on human T-cell lines but also against virus grown on macaque peripheral blood mononuclear cells (PBMC). The breadth of protection, however, was limited. In three experiments, 3 of 10 animals challenged with the parental uncloned SIVmne were completely protected. Of the remaining animals, three were transiently virus positive and four were persistently positive after challenge, as were 10 nonimmunized control animals. Protection was not correlated with levels of serum-neutralizing antibodies against the homologous SIVmne or a related virus, SIVmac251. To gain further insight into the protective mechanism, we analyzed nucleotide sequences in the envelope region of the uncloned challenge virus and compared them with those present in the PBMC of infected animals. The majority (85%) of the uncloned challenge virus was homologous to the molecular clone from which the vaccines were made (E11S type). The remaining 15% contained conserved changes in the V1 region (variant types). Control animals infected with this uncloned virus had different proportions of the two genotypes, whereas three of four immunized but persistently infected animals had >99% of the variant types early after infection. These results indicate that the protective immunity elicited by recombinant gp160 vaccines is restricted primarily to the homologous virus and suggest the possibility that immune responses directed to the V1 region of the envelope protein play a role in protection.

* Corresponding author. Present address: Department of Pharmaceutics and Regional Primate Research Center, Box 357331, University of Washington, Seattle, WA 98195. Phone: (206) 616-9764. Fax: (206) 543-3204. E-mail: hus{at}u.washington.edu.

dagger Present address: Sequim, WA 98382.

Dagger Present address: Corixa Corp., Seattle, WA 98104.

Journal of Virology, January 1999, p. 618-630, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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