A new approach to AIDS research and prevention: the use of gene-mutated HIV-1/SIV chimeric viruses for anti-HIV-1 live-attenuated vaccines.
The lack of a suitable animal model is a major obstacle to developing anti-HIV-1 vaccines. We successfully generated an SIVmac/HIV-1 chimeric virus (SHIV) (designated as NM-3rN) that contains the HIV-1 env gene and is infectious to macaque monkeys. Challenging the vaccinated macaque monkeys with NM-3rN, we developed an evaluation system for anti-HIV-1 Env-targeted vaccines. For the purpose of making the vaccine, a series of gene-mutated SHIVs were constructed. The monkeys vaccinated with these SHIVs had long-term anti-virus immunities without manifesting the disease, and became resistant to a challenge inoculation with NM-3rN. The sera from a monkey showed that, after the vaccination, the neutralizing antibodies not only against the parental HIV-1 but also against an antigenically different HIV-1 were raised. In vivo experiments confirmed that the vaccinated monkeys were protected from the challenge inoculum of an antigenically different SHIV-MN. Vaccination of monkeys with the attenuated SHIVs showed that further gene-deletion of the SHIV resulted in less immunogenicity. Nevertheless, the attenuated SHIVs had a vaccine effect against the challenge inoculation. In addition to specific immunities including neutralizing antibodies and cytotoxic T cells, a more complicated immune mechanism induced by live vaccine appears to play a role in this protection. Our data suggest that the live vaccine can induce strong and wide-range immunity against HIV-1. These SHIVs should contribute to understanding the pathogenicity of AIDS and to the development of future anti-HIV-1 live vaccines for humans.
Haga
T
T
Laboratory of Pathogenic Virus, Institute for Virus Research, Kyoto University, Japan.
Kuwata
T
T
Ui
M
M
Igarashi
T
T
Miyazaki
Y
Y
Hayami
M
M
D016915:AIDS Vaccines; D000163:Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D000818:Animals; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014613:Vaccines, Attenuated
D016915:AIDS Vaccines; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated