Combined intrarectal/intradermal inoculation of recombinant Mycobacterium bovis bacillus Calmette–Guérin (BCG) induces enhanced immune responses against the inserted HIV-1 V3 antigen

• Published in: Vaccine 2002-12, Vol.21 (3), p.158-166
• Main Authors: Kawahara, Mamoru, Matsuo, Kazuhiro, Nakasone, Tadashi, Hiroi, Takachika, Kiyono, Hiroshi, Matsumoto, Sohkichi, Yamada, Takeshi, Yamamoto, Naoki, Honda, Mitsuo
• Format: Article
• Language: English
• Subjects: Administration, Rectal; AIDS Vaccines - immunology; Animals; Antibodies, Viral - blood; BCG; BCG Vaccine - immunology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Gene expression; Genetic Vectors; Guinea Pigs; HIV; HIV Antibodies - biosynthesis; HIV Antigens - immunology; HIV-1; HIV-1 - immunology; Hogs; Human immunodeficiency virus; Human immunodeficiency virus 1; Hypersensitivity; Immunization; Injections, Intradermal; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Lymphocytes; Microbiology; Mycobacterium bovis; Mycobacterium bovis - genetics; Neutralization; Peptides; Proteins; Public health; Recombinant BCG vaccine; Recombinant Proteins - immunology; Rodents; Swine; Th1 Cells - immunology; Tuberculosis; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(02)00465-6

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 α-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 IFNγ 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.