Rectal and vaginal immunization with a macromolecular multicomponent peptide vaccine candidate for HIV-1 infection induces HIV-specific protective immune responses.
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.
Kato
H
H
Department of Bacteriology, Yokohama City University School of Medicine, Japan.
Bukawa
H
H
Hagiwara
E
E
Xin
K Q
KQ
Hamajima
K
K
Kawamoto
S
S
Sugiyama
M
M
Sugiyama
M
M
Noda
E
E
Nishizaki
M
M
Okuda
K
K
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*
D016915:AIDS Vaccines; D001704:Biopolymers; D015483:HIV Antibodies; D007071:Immunoglobulin A, Secretory; D010455:Peptides; D014614:Vaccines, Synthetic