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1 October 1995

Vaccine-induced protection of chimpanzees against infection by a heterologous human immunodeficiency virus type 1

Abstract

The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1) is a major problem to overcome in the development of an effective vaccine. In the most reliable animal model of HIV-1 infection, chimpanzees were immunized with various combinations of HIV-1 antigens, which were derived primarily from the surface glycoprotein, gp160, of HIV-1 strains LAI and MN. The immunogens also included a live recombinant canarypox virus expressing a gp160-MN protein. In one experiment, two chimpanzees were immunized multiple times; one animal received antigens derived only from HIV-1LAI, and the second animal received antigens from both HIV-1LAI and HIV-1MN. In another experiment, four chimpanzees were immunized in parallel a total of five times over 18 months; two animals received purified gp160 and V3-MN peptides, whereas the other two animals received the recombinant canarypox virus and gp160. At 3 months after the final booster, all immunized and naive control chimpanzees were challenged by intravenous inoculation of HIV-1SF2; therefore, the study represented an intrasubtype B heterologous virus challenge. Virologic and serologic follow-up showed that the controls and the two chimpanzees immunized with the live recombinant canarypox virus became infected, whereas the other animals that were immunized with gp160 and V3-MN peptides were protected from infection. Evaluation of both cellular and humoral HIV-specific immune responses at the time of infectious HIV-1 challenge identified the following as possible correlates of protection: antibody titers to the V3 loop of MN and neutralizing antibody titers to HIV-1MN or HIV-1LAI, but not to HIV-1SF2. The results of this study indicate that vaccine-mediated protection against intravenous infection with heterologous HIV-1 strains of the same subtype is possible with some immunogens.

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Published In

cover image Journal of Virology
Journal of Virology
Volume 69Number 10October 1995
Pages: 6239 - 6248
PubMed: 7666524

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Published online: 1 October 1995

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Authors

M Girard
Institut Pasteur, Paris, France.
B Meignier
Institut Pasteur, Paris, France.
F Barré-Sinoussi
Institut Pasteur, Paris, France.
M P Kieny
Institut Pasteur, Paris, France.
T Matthews
Institut Pasteur, Paris, France.
E Muchmore
Institut Pasteur, Paris, France.
P L Nara
Institut Pasteur, Paris, France.
Q Wei
Institut Pasteur, Paris, France.
L Rimsky
Institut Pasteur, Paris, France.
K Weinhold
Institut Pasteur, Paris, France.

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