title: Combined intrarectal/intradermal inoculation of recombinant Mycobacterium bovis bacillus Calmette-Guérin (BCG) induces enhanced immune responses against the inserted HIV-1 V3 antigen.
abstract: The development of a successful recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) vector-based vaccine for human immunodeficiency virus type 1 (HIV-1) requires the induction of high levels of HIV-1-specific immunity while at the same time maintaining immunity to tuberculosis. To examine a combined vaccination strategy for enhancement of immune responses specific for HIV-1, guinea pigs were inoculated with either a single or combination intradermal (i.d.), intrarectal (i.r.) and intranasal (i.n.) administration of rBCG-pSOV3J1 which secretes a chimeric protein of HIV-1 V3J1 peptide and alpha-antigen. Significant level of delayed-type hypersensitivity to both V3J1 peptide and tuberculin was induced in guinea pigs inoculated with human doses of rBCG-pSOV3J1 by a combination of intrarectal and intradermal routes. Guinea pigs inoculated by combined routes also had significantly higher titers of HIV-1-specific serum IgG and IgA compared with those animals immunized only intrarectally, which led to the enhanced neutralization activity against HIV-1(MN). In addition, the induction of high levels of IFNgamma and interleukin-2 (IL-2) mRNA in PBMC, splenocytes, and intraepithelial lymphocytes from the immunized animals was detected until at least 110 weeks post-inoculation. These results suggest that enhanced immune responses specific for HIV-1 are efficiently induced by combined intrarectal and intradermal immunization with rBCG-HIV, and antigen-specific Th1-type memory cells are maintained for more than 2 years in the immunized animals. Thus, inoculation with rBCG-HIV by combined routes represents an effective vaccination strategy to elicit high levels of HIV-1-specific immune responses.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kawahara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakasone
authors.forename: Takachika
authors.initials: T
authors.lastname: Hiroi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.forename: Sohkichi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Honda
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000285:Administration, Rectal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001500:BCG Vaccine / Q000276:immunology*; D005822:Genetic Vectors; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000096:biosynthesis*; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D009163:Mycobacterium bovis / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D001500:BCG Vaccine; D015483:HIV Antibodies; D015488:HIV Antigens; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma