title: Highly attenuated rabies virus-based vaccine vectors expressing simian-human immunodeficiency virus89.6P Env and simian immunodeficiency virusmac239 Gag are safe in rhesus macaques and protect from an AIDS-like disease.
abstract: We analyzed the safety and immunogenicity of attenuated rabies virus vectors expressing simian-human immunodeficiency virus (SHIV)-1(89.6P) Env or simian immunodeficiency virus (SIV)(mac239) Gag in rhesus macaques. Four test macaques were immunized with both vaccine constructs, and 2 control macaques received an empty rabies vector. Seroconversion against rabies virus glycoprotein (G) and SHIV(89.6P) Env was detected after the initial immunization, but no cellular responses against SHIV antigens were observed. HIV/SIV-specific immune responses were not enhanced by boosts with the same vectors. Therefore, we constructed vectors expressing SHIV(89.6P) Env and SIV(mac239) Gag in which the rabies G was replaced with the G protein of vesicular stomatitis virus (VSV). Two years after initial immunization, a boost with the rabies-VSV G vectors resulted in SIV/HIV-specific immune responses. Upon challenge with SHIV(89.6P) test macaques controlled the infection, whereas control macaques had high levels of viremia and a profound loss of CD4(+) T cells, with 1 control macaque dying of an AIDS-like disease.
authors.affiliation: Department of Microbiology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Philip M
authors.initials: PM
authors.lastname: McKenna
authors.forename: Martin L
authors.initials: ML
authors.lastname: Koser
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Carlson
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Amy B
authors.initials: AB
authors.lastname: Papaneri
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Pomerantz
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dietzschold
authors.forename: Peter
authors.initials: P
authors.lastname: Silvera
authors.forename: James P
authors.initials: JP
authors.lastname: McGettigan
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Schnell
mesh_terms: D000818:Animals; D017931:DNA Primers; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D008253:Macaca mulatta; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D011820:Rabies virus / Q000235:genetics; D018449:SAIDS Vaccines / Q000627:therapeutic use*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
chemical_list: D017931:DNA Primers; D015686:Gene Products, env; D015683:Gene Products, gag; D012367:RNA, Viral; D018449:SAIDS Vaccines; D014614:Vaccines, Synthetic