Vaccine induction of antibodies and tissue-resident CD8+ T cells enhances protection against mucosal SHIV-infection in young macaques
| Autor: | John P. Vasilakos, Rafiq Nabi, Dan H. Barouch, Yevgeniy Kovalenkov, Sudhir Pai Kasturi, Pamela A. Kozlowski, Traci Legere, Bali Pulendran, Jonathan W. Yewdell, David C. Montefiori, Jens Wrammert, James S. Gibbs, Parin Patel, Lori M. Spicer, Mark A. Tomai, Pradeep B. J. Reddy, Eric Hunter, Barton F. Haynes, C. Yong Kang, Clare F. Quarnstrom, David Masopust, Caroline Petitdemange, Cynthia A. Derdeyn, Celia C. LaBranche, Francois Villinger, Rama Rao Amara |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
T cell viruses Genetic Vectors Simian Acquired Immunodeficiency Syndrome HIV Infections Biology CD8-Positive T-Lymphocytes Antibodies Viral 03 medical and health sciences 0302 clinical medicine Immunogenicity Vaccine Adjuvants Immunologic medicine Cytotoxic T cell Animals AIDS Vaccines Vaccines Synthetic Mucous Membrane Vaccination Antibody titer env Gene Products Human Immunodeficiency Virus General Medicine Acquired immune system biology.organism_classification Virology Antibodies Neutralizing Macaca mulatta Disease Models Animal 030104 developmental biology medicine.anatomical_structure Treatment Outcome Immunization Vesicular stomatitis virus 030220 oncology & carcinogenesis Vagina biology.protein HIV-1 Female Simian Immunodeficiency Virus Antibody Heterocyclic Compounds 3-Ring CD8 Stearic Acids Research Article |
| Zdroj: | JCI insight. 4(4) |
| ISSN: | 2379-3708 |
| Popis: | Antibodies and cytotoxic T cells represent 2 arms of host defense against pathogens. We hypothesized that vaccines that induce both high-magnitude CD8(+) T cell responses and antibody responses might confer enhanced protection against HIV. To test this hypothesis, we immunized 3 groups of nonhuman primates: (a) Group 1, which includes sequential immunization regimen involving heterologous viral vectors (HVVs) comprising vesicular stomatitis virus, vaccinia virus, and adenovirus serotype 5–expressing SIVmac239 Gag; (b) Group 2, which includes immunization with a clade C HIV-1 envelope (Env) gp140 protein adjuvanted with nanoparticles containing a TLR7/8 agonist (3M-052); and (c) Group 3, which includes a combination of both regimens. Immunization with HVVs induced very high–magnitude Gag-specific CD8(+) T cell responses in blood and tissue-resident CD8(+) memory T cells in vaginal mucosa. Immunization with 3M-052 adjuvanted Env protein induced robust and persistent antibody responses and long-lasting innate responses. Despite similar antibody titers in Groups 2 and 3, there was enhanced protection in the younger animals in Group 3, against intravaginal infection with a heterologous SHIV strain. This protection correlated with the magnitude of the serum and vaginal Env-specific antibody titers on the day of challenge. Thus, vaccination strategies that induce both CD8(+) T cell and antibody responses can confer enhanced protection against infection. |
| Databáze: | OpenAIRE |
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