Vaccine-induced protection of chimpanzees against infection by a heterologous human immunodeficiency virus type 1.
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.
Girard
M
M
Institut Pasteur, Paris, France.
Meignier
B
B
Barré-Sinoussi
F
F
Kieny
M P
MP
Matthews
T
T
Muchmore
E
E
Nara
P L
PL
Wei
Q
Q
Rimsky
L
L
Weinhold
K
K
D016915:AIDS Vaccines / Q000276:immunology*; D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000821:virology; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D015726:Giant Cells; D015483:HIV Antibodies / Q000097:blood*; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D015151:Immunoblotting; D008297:Male; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D016133:Polymerase Chain Reaction / Q000379:methods; D013045:Species Specificity; D013997:Time Factors
D016915:AIDS Vaccines; D017931:DNA Primers; D004279:DNA, Viral; D015483:HIV Antibodies; D015488:HIV Antigens