title: Immunogenicity and safety of the vaccinia virus LC16m8Δ vector expressing SIV Gag under a strong or moderate promoter in a recombinant BCG prime-recombinant vaccinia virus boost protocol.
abstract: We compared the effect of the very strong pSFJ1-10 and moderately strong p7.5 promoters on the immunogenicity and pathogenicity of the replication-competent vaccinia virus (VV) LC16m8Δ (m8Δ) vector harboring the SIV gag gene in a vaccination regimen consisting of a recombinant BCG-SIVGag (rBCG-SIVGag) prime followed by a recombinant vaccinia boost. m8Δ/pSFJ/SIVGag synthesized more Gag protein than m8Δ/p7.5/SIVGag but replicated less efficiently in vitro. In addition, m8Δ/pSFJ/SIVGag was less pathogenic and elicited Gag-specific IFN-γ(+), CD107a(+), CD8(+) cells more efficiently than m8Δ/p7.5/SIVGag. Vaccination by this regimen elicited long-lasting Gag-specific CD8(+) T cells, the majority of which showed a CCR7(-) phenotype at over 8 weeks post-boost. Tetramer staining analyses revealed maintenance of Gag specific tetramer(+), CD62L(-), CD8(+) T cells for long time in vaccinated mice. However, Gag expression increased the neurotoxicity of the vaccinia vector, indicating the necessity of safety testing for each recombinant VV. We propose that this recombinant BCG prime-m8Δ/pSFJ/HIVGag boost regimen would be a promising vaccination procedure for preventing HIV infection.
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sato
authors.forename: Chen
authors.initials: C
authors.lastname: Jing
authors.forename: Mao
authors.initials: M
authors.lastname: Isshiki
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Minoru
authors.initials: M
authors.lastname: Kidokoro
authors.forename: Shiki
authors.initials: S
authors.lastname: Takamura
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohashi
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Shida
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D001500:BCG Vaccine / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D019041:L-Selectin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D011401:Promoter Regions, Genetic; D011817:Rabbits; D054400:Receptors, CCR7 / Q000378:metabolism; D012900:Smallpox Vaccine / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D001500:BCG Vaccine; C515371:Ccr7 protein, mouse; C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D054400:Receptors, CCR7; D012900:Smallpox Vaccine; D014614:Vaccines, Synthetic; D019041:L-Selectin
keywords: CTL; HIV; Recombinant BCG; Recombinant vaccinia; SIV