Multiple immunizations with attenuated poxvirus HIV type 2 recombinants and subunit boosts required for protection of rhesus macaques.
Vaccine protocols involving multiple immunizations with molecularly attenuated vaccinia virus (NYVAC) or naturally attenuated canarypox virus (ALVAC) HIV-2 recombinants and subunit boosts have conferred longlasting protection against HIV-2 infection of macaques. Similar complex protocols using HIV-1 NYVAC and ALVAC recombinants and subunit boosts have provided cross-protection against HIV-2 challenge. Here a simplified three-immunization regimen over 24 weeks was tested in 18 juvenile rhesus macaques. Twelve macaques were immunized twice with NYVAC or ALVAC recombinants carrying HIV-2 env, gag, and pol genes. Subsequently, macaques in groups of three received either an additional recombinant immunization or an HIV-2 gp160 boost. Six control macaques received three immunizations of NYVAC or ALVAC vector alone and additionally alum at the third immunization. Macaques primed with ALVAC recombinant exhibited sporadic T cell proliferative activity, and all but one failed to develop neutralizing antibodies. In contrast, macaques primed with NYVAC recombinants had no T cell proliferative activity but exhibited neutralizing antibody titers (highest in the three recombinant group) that declined by the time of challenge. None of the macaques exhibited significant cytotoxic T lymphocyte activity. Following challenge at 32 weeks with HIV-2SBL6669 all macaques became infected. Thus, the three-immunization regimen is not sufficient to confer protective immunity in the HIV-2 rhesus macaque model. However, delayed infection in macaques immunized with the NYVAC-HIV-2 recombinant may have been associated with the development of memory B cells capable of providing a neutralizing antibody response on challenge.
Myagkikh
M
M
Laboratory of Tumor Cell Biology, DBS, NCI, NIH, Bethesda, Maryland 20892-4255, USA.
Alipanah
S
S
Markham
P D
PD
Tartaglia
J
J
Paoletti
E
E
Gallo
R C
RC
Franchini
G
G
Robert-Guroff
M
M
D016915:AIDS Vaccines / Q000627:therapeutic use*; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000818:Animals; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology; D015498:HIV-2 / Q000276:immunology*; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D008253:Macaca mulatta; D011994:Recombinant Proteins / Q000627:therapeutic use; D014613:Vaccines, Attenuated / Q000627:therapeutic use*; D014616:Vaccinia virus; D014765:Viral Vaccines / Q000627:therapeutic use*
D016915:AIDS Vaccines; C078788:ALVAC vaccine; D000956:Antigens, Viral; C078787:NYVAC vaccine; D011994:Recombinant Proteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines