Adenovirus-Human Immunodeficiency Virus (HIV) Envelope Recombinant Vaccines Elicit High-Titered HIV-Neutralizing Antibodies in the Dog Model

• Published in: Proceedings of the National Academy of Sciences - PNAS 1992-08, Vol.89 (16), p.7777-7781
• Main Authors: Natuk, Robert J., Chanda, Pranab K., Lubeck, Michael D., Davis, Alan R., Wilhelm, James, Hjorth, Richard, Wade, Mark S., Bhat, Bheem M., Mizutani, Satoshi, Lee, Sally, Eichberg, Jorg, Gallo, Robert C., Hung, paul P., Robert-Guroff, Marjorie
• Format: Article
• Language: English
• Subjects: adenovirus; Adenoviruses, Human - genetics; Adenoviruses, Human - immunology; AIDS Vaccines - immunology; AIDS/HIV; Animals; Antibodies; Antibody Formation; Antigens; Biological and medical sciences; Blotting, Western; Dogs; Enzyme linked immunosorbent assay; Fundamental and applied biological sciences. Psychology; Gene Products, env - immunology; HIV; HIV Antibodies - analysis; HIV Antibodies - biosynthesis; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp160; HIV-1 - genetics; HIV-1 - immunology; human immunodeficiency virus; Immunity (Disease); Immunization; Infections; Inoculation; Medical research; Microbiology; Neutralization Tests; Neutralizing antibodies; Protein Precursors - immunology; Recombination, Genetic; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - immunology; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Vaccines - immunology; Virology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.16.7777

Recombinant human adenoviruses (Ads) (types 4, 5, and 7) expressing the HIV-1 envelope membrane glycoprotein (gp160) were tested for immunogenicity in the dog. Administration of recombinant Ad7-env by intratracheal inoculation resulted in a low serum antibody response to gp160, which developed over several weeks. A strong neutralizing antibody response to the Ad7 vector developed within 1 week of infection. A subsequent booster inoculation 12 weeks later with the heterotypic Ad4-env recombinant virus resulted in significantly enhanced humoral responses directed at the envelope antigen, as measured by both ELISA and Western blot analysis as well as high-titer type-specific neutralizing antibodies, with some animals achieving neutralization titers approaching 1000. Recombinant HIV envelope glycoprotein derived from Ad-HIV-infected cell cultures was used as a subunit booster injection for dogs that had previously received sequential immunizations with heterotypic recombinant Ads. Significant immune responses against the envelope developed as measured by ELISA, Western blot analysis, and neutralization assays. These data indicate that live recombinant Ad-HIV vaccines are capable of inducing high-titer type-specific neutralizing antibodies to gp160 in vivo. Recombinant HIV envelope glycoprotein subunit vaccines, prepared from Ad-envinfected cells, are capable of boosting these responses.