Polygene DNA vaccine induces a high level of protective effect against HIV-vaccinia virus challenge in mice.
Single HIV-1 subtype DNA vaccine is unlikely to provide reactive protection across a wide range of HIV strains since the HIV virus changes the antigenic sites, particularly, in env gene. To overcome these issues, we constructed a multivalent poly-epitope DNA vaccine. A polygenic DNA vaccine encoding 20 antigenic epitopes from the HIV-1 Env, Gag, and Pol proteins of several clades was constructed using humanized and optimized codons and it was named here hDNA vaccine. In mice, this hDNA vaccine stimulated the following strong (1) antigen-specific serum antibody (Ab) responses, (2) delayed-type hypersensitivity, (3) the activation of IFN-gamma secretion cells targeting gp120 and synthetic antigenic peptides, in addition (4) a significant level of several peptide specific cytotoxic T lymphocytes (CTL) responses. Challenged with modified vaccinia viruses vPE16 and vP1206 expressing HIV-1 env and gag.pol genes, respectively, demonstrated the viral titers in the ovary of the mice vaccinated with hDNA significantly less compared to the unvaccinated mice. Thus, the use of polygene DNA vaccine appears to induce a high level of HIV-specific immune responses and is very effective against challenge with recombinant HIV-vaccinia viruses.
Department of Bacteriology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Kaori
K
Shinoda
Ke-Qin
KQ
Xin
Nao
N
Jounai
Yoshitsugu
Y
Kojima
Yuichi
Y
Tamura
Eiichi
E
Okada
Susumu
S
Kawamoto
Katsuji
K
Okuda
Dennis
D
Klinman
Kenji
K
Okuda
D016915:AIDS Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015683:Gene Products, gag / Q000276:immunology; D015483:HIV Antibodies / Q000032:analysis / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007091:Image Processing, Computer-Assisted; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*
D016915:AIDS Vaccines; D016207:Cytokines; D015683:Gene Products, gag; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D007371:Interferon-gamma