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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,
James E.
Klaniecki,2,
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.

Present address: Sequim, WA
98382.

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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