title: Protective efficacy of nonpathogenic nef-deleted SHIV vaccination combined with recombinant IFN-gamma administration against a pathogenic SHIV challenge in rhesus monkeys.
abstract: We previously reported that a nef-deleted SHIV (SHIV-NI) is nonpathogenic and gave macaques protection from challenge infection with pathogenic SHIV-C2/1. To investigate whether IFN-gamma augments the immune response induced by this vaccination, we examined the antiviral and adjuvant effect of recombinant human IFN-gamma (rIFN-gamma) in vaccinated and unvaccinated monkeys. Nine monkeys were vaccinated with nef-deleted nonpathogenic SHIV-NI. Four of them were administered with rIFN-gamma and the other five monkeys were administered with placebo. After the challenge with pathogenic SHIV-C2/1, CD4(+) T-cell counts were maintained similarly in monkeys of both groups, while those of the unvaccinated monkeys decreased dramatically at 2 weeks after challenge. However, the peaks of plasma viral load were reduced to 100-fold in SHIV-NI vaccinated monkeys combined with rIFN-gamma compared with those in SHIV-NI vaccinated monkeys without rIFN-gamma. The peaks of plasma viral load were inversely correlated with the number of SIV Gag-specific IFN-gamma-producing cells. In SHIV-NI-vaccinated monkeys with rIFN-gamma, the number of SIV Gag-specific IFN-gamma-producing cells of PBMCs increased 2-fold compared with those in SHIV-NI-vaccinated monkeys without rIFN-gamma, and the NK activity and MIP-1alpha production of PBMCs were also enhanced. Thus, vaccination of SHIV-NI in combination with rIFN-gamma was more effective in modulating the antiviral immune system into a Th1 type response than SHIV-NI vaccination alone. These results suggest that IFN-gamma augmented the anti-viral effect by enhancing innate immunity and shifting the immune response to Th1.
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto, Kyoto 606-8507, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kaneyasu
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kita
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Ohkura
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ibuki
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Enose
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sato
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Masanori
authors.initials: M
authors.lastname: Hayami
mesh_terms: D000818:Animals; D017353:Gene Deletion; D015754:Genes, nef / Q000235:genetics; D006678:HIV / Q000276:immunology*; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology*; D008253:Macaca mulatta; D016865:Reassortant Viruses / Q000276:immunology*; D011994:Recombinant Proteins; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D014765:Viral Vaccines
chemical_list: D011994:Recombinant Proteins; D018449:SAIDS Vaccines; D014765:Viral Vaccines; D007371:Interferon-gamma