title: Rectal and vaginal immunization with a macromolecular multicomponent peptide vaccine candidate for HIV-1 infection induces HIV-specific protective immune responses.
abstract: An effective vaccine for human immunodeficiency virus (HIV) is needed to stimulate the immune response of the genital mucus to prevent mucosal transmission of the virus. We have developed a macromolecular multicomponent peptide vaccine candidate, VC1. Both rectal and vaginal immunization of VC1 mixed with cholera toxin (CT) induced HIV-1-specific IgA antibody in mouse fecal extract solution and vaginal wash. These antibody productions were enhanced by the combination with IL-4 or GM-CSF expressing plasmids. Either fecal extract or vaginal wash solution from immunized mice inhibited production of HIV-1IIIB p24 protein. The mononuclear cells from spleen, intestinal lymph nodes, or Peyer's patches from VC1- and CT-immunized mice released IFN-gamma or IL-4, when these cells were co-cultured with VC1 antigen. In addition, the regional lymphoid cells from rectal and vaginal region of mice immunized with VC1 and CT also elicited a substantial level of HIV-1-specific cytotoxic T cell (CTL) response. This CTL response was enhanced by the addition of IL-12 expressing plasmid. Our results clearly demonstrated that both rectal and vaginal immunization could induce systemic and mucosal immunities specific for HIV-1.
authors.affiliation: Department of Bacteriology, Yokohama City University School of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Bukawa
authors.forename: E
authors.initials: E
authors.lastname: Hagiwara
authors.forename: K Q
authors.initials: KQ
authors.lastname: Xin
authors.forename: K
authors.initials: K
authors.lastname: Hamajima
authors.forename: S
authors.initials: S
authors.lastname: Kawamoto
authors.forename: M
authors.initials: M
authors.lastname: Sugiyama
authors.forename: M
authors.initials: M
authors.lastname: Sugiyama
authors.forename: E
authors.initials: E
authors.lastname: Noda
authors.forename: M
authors.initials: M
authors.lastname: Nishizaki
authors.forename: K
authors.initials: K
authors.lastname: Okuda
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000282:Administration, Intravaginal; D000285:Administration, Rectal; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001704:Biopolymers / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*; D012007:Rectum / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*; D014621:Vagina / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D001704:Biopolymers; D015483:HIV Antibodies; D007071:Immunoglobulin A, Secretory; D010455:Peptides; D014614:Vaccines, Synthetic