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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
Author(s) -
Haga Takeshi,
Kuwata Takeo,
Ui Masahiro,
Igarashi Tatsuhiko,
Miyazaki Yasuyuki,
Hayami Masanori
Publication year - 1998
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.1998.tb02279.x
Subject(s) - virology , immunogenicity , biology , hiv vaccine , vaccination , simian immunodeficiency virus , macaque , lentivirus , aids vaccines , attenuated vaccine , antibody , immunity , immune system , virus , neutralizing antibody , immunology , gene , viral disease , vaccine trial , virulence , genetics , paleontology
Abstract 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.