title: Effects of different promoters on the virulence and immunogenicity of a HIV-1 Env-expressing recombinant vaccinia vaccine.
abstract: Previously, we developed a vaccination regimen that involves priming with recombinant vaccinia virus LC16m8Δ (rm8Δ) strain followed by boosting with a Sendai virus-containing vector. This protocol induced both humoral and cellular immune responses against the HIV-1 envelope protein. The current study aims to optimize this regimen by comparing the immunogenicity and safety of two rm8Δ strains that express HIV-1 Env under the control of a moderate promoter, p7.5, or a strong promoter, pSFJ1-10. m8Δ-p7.5-JRCSFenv synthesized less gp160 but showed significantly higher growth potential than m8Δ-pSFJ-JRCSFenv. The two different rm8Δ strains induced antigen-specific immunity; however, m8Δ-pSFJ-JRCSFenv elicited a stronger anti-Env antibody response whereas m8Δ-p7.5-JRCSFenv induced a stronger Env-specific cytotoxic T lymphocyte response. Both strains were less virulent than the parental m8Δ strain, suggesting that they would be safe for use in humans. These findings indicate the vaccine can be optimized to induce favorable immune responses (either cellular or humoral), and forms the basis for the rational design of an AIDS vaccine using recombinant vaccinia as the delivery vector.
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Isshiki
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan. Electronic address: zhangxf@igm.hokudai.ac.jp.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Sato
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohashi
authors.affiliation: DNAVEC Corporation, Techno Park Oho, 6 Ohkubo, Tsukuba, Ibaraki 300-2611, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Shida
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D011817:Rabbits; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D014614:Vaccines, Synthetic; C514797:gp160 protein, Human immunodeficiency virus 1
keywords: HIV-1 Env; Immunogenicity; LC16m8Δ; Promoter p7.5; Promoter pSFJ1-10; Safety