Antibodies with High Avidity to the gp120 Envelope Protein in Protection from Simian Immunodeficiency Virus SIV mac251 Acquisition in an Immunization Regimen That Mimics the RV-144 Thai Trial
| Autor: | Ranajit Pal, Poonam Pegu, Georgia D. Tomaras, Guido Ferrari, Nelson L. Michael, Yongjun Guan, Mangala Rao, Monica Vaccari, Jeffrey D. Lifson, Jim Tartaglia, David Venzon, Jerome H. Kim, Maria Grazia Ferrari, S. Munir Alam, Melvin N. Doster, Brandon F. Keele, Lauren Hudacik, Shari N. Gordon, David C. Montefiori, Claudio Fenizia, Erik Billings, Genoveffa Franchini, Stephen Whitney, Donald Stablein |
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| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
viruses Immunology Antibody Affinity Simian Acquired Immunodeficiency Syndrome CD8-Positive T-Lymphocytes Biology Antibodies Viral medicine.disease_cause Microbiology Virus Viral Envelope Proteins Virology Vaccines and Antiviral Agents medicine Animals Avidity RV 144 Membrane Glycoproteins SAIDS Vaccines virus diseases Simian immunodeficiency virus Vaccination Immunization Insect Science biology.protein Macaca Antibody |
| Zdroj: | Journal of Virology. 87:1708-1719 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | The recombinant canarypox vector, ALVAC-HIV, together with human immunodeficiency virus (HIV) gp120 envelope glycoprotein, has protected 31.2% of Thai individuals from HIV acquisition in the RV144 HIV vaccine trial. This outcome was unexpected, given the limited ability of the vaccine components to induce CD8 + T-cell responses or broadly neutralizing antibodies. We vaccinated macaques with an immunization regimen intended to mimic the RV144 trial and exposed them intrarectally to a dose of the simian immunodeficiency virus SIV mac251 that transmits few virus variants, similar to HIV transmission to humans. Vaccination induced anti-envelope antibodies in all vaccinees and CD4 + and CD8 + T-cell responses. Three of the 11 macaques vaccinated with ALVAC-SIV/gp120 were protected from SIV mac251 acquisition, but the result was not significant. The remaining vaccinees were infected and progressed to disease. The magnitudes of vaccine-induced SIV mac251 -specific T-cell responses and binding antibodies were not significantly different between protected and infected animals. However, sera from protected animals had higher avidity antibodies to gp120, recognized the variable envelope regions V1/V2, and reduced SIV mac251 infectivity in cells that express high levels of α 4 β 7 integrins, suggesting a functional role of antibodies to V2. The current results emphasize the utility of determining the titer of repeated mucosal challenge in the preclinical evaluation of HIV vaccines. |
| Databáze: | OpenAIRE |
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