title: Induction of protective immunity against pathogenic simian immunodeficiency virus by a foreign receptor-dependent replication of an engineered avirulent virus.
abstract: In AIDS vaccine strategies, live attenuated vaccines can confer good resistance against pathogenic virus infections but have the potential risk of inducing disease, whereas safer replication-negative strategies such as DNA vaccinations have so far failed to prevent the disease onset. Here, we developed a novel DNA vaccine strategy to induce restricted replication of an avirulent virus and evaluated it in a simian immunodeficiency virus (SIV) infection model. We generated a chimeric SIV, FMSIV, by replacing SIV env with ecotropic Friend murine leukemia virus (FMLV) env to confine its replication to FMLV receptor (mCAT1)-expressing cells. In primate cells lacking mCAT1, FMSIV did not replicate unless mCAT1 was introduced exogenously. Vaccination to macaques with both the FMSIV DNA and the mCAT1-expression plasmid DNA induced SIV Gag-specific cellular immune responses and resistance against pathogenic SIV(mac239) challenge more efficiently than the replication-negative control vaccination with the FMSIV DNA alone. This strategy may be useful for development of safe and effective vaccines against various kinds of pathogenic viruses.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-murayama, 208-0011, Tokyo, Japan. matano@nih.go.jp
authors.forename: T
authors.initials: T
authors.lastname: Matano
authors.forename: M
authors.initials: M
authors.lastname: Kano
authors.forename: T
authors.initials: T
authors.lastname: Odawara
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Takeda
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: T
authors.initials: T
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Nagai
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D005622:Friend murine leukemia virus / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma