Mucosal vaccine efficacy against intrarectal SHIV is independent of anti-Env antibody response
| Autor: | John D. Clements, David Venzon, Thomas Musich, Dennis M. Klinman, Robert C. Waters, Blake Frey, Timothy R. Fouts, Yichuan Wang, James Talton, George K. Lewis, Jay A. Berzofsky, Giorgio Trinchieri, Kurt Berckmueller, Yongjun Sui, Genoveffa Franchini, Venkatramanan Mohanram, Amiran Dzutsev, James F. Kirk, Anthony L. DeVico, Diego A. Vargas-Inchaustegui, Georgia D. Tomaras, Xiaoying Shen, Robert C. Gallo, Marjorie Robert-Guroff |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Cellular immunity Colon viruses Population Simian Acquired Immunodeficiency Syndrome 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immunity Medicine Animals HIV vaccine Intestinal Mucosa education Immunity Mucosal AIDS Vaccines education.field_of_study Acquired Immunodeficiency Syndrome Immunity Cellular biology business.industry Rectum SAIDS Vaccines virus diseases General Medicine Macaca mulatta 030104 developmental biology chemistry 030220 oncology & carcinogenesis Immunology biology.protein HIV-1 Simian Immunodeficiency Virus Vaccinia Antibody business Viral load Ex vivo Research Article |
| Zdroj: | The Journal of clinical investigation. 129(3) |
| ISSN: | 1558-8238 |
| Popis: | It is widely believed that protection against acquisition of HIV or SIV infection requires anti-envelope (anti-Env) antibodies, and that cellular immunity may affect viral loads but not acquisition, except in special cases. Here we provide evidence to the contrary. Mucosal immunization may enhance HIV vaccine efficacy by eliciting protective responses at portals of exposure. Accordingly, we vaccinated macaques mucosally with HIV/SIV peptides, modified vaccinia Ankara–SIV (MVA-SIV), and HIV-gp120–CD4 fusion protein plus adjuvants, which consistently reduced infection risk against heterologous intrarectal SHIV(SF162P4) challenge, both high dose and repeated low dose. Surprisingly, vaccinated animals exhibited no anti-gp120 humoral responses above background and Gag- and Env-specific T cells were induced but failed to correlate with viral acquisition. Instead, vaccine-induced gut microbiome alteration and myeloid cell accumulation in colorectal mucosa correlated with protection. Ex vivo stimulation of the myeloid cell–enriched population with SHIV led to enhanced production of trained immunity markers TNF-α and IL-6, as well as viral coreceptor agonist MIP1α, which correlated with reduced viral Gag expression and in vivo viral acquisition. Overall, our results suggest mechanisms involving trained innate mucosal immunity together with antigen-specific T cells, and also indicate that vaccines can have critical effects on the gut microbiome, which in turn can affect resistance to infection. Strategies to elicit similar responses may be considered for vaccine designs to achieve optimal protective efficacy. |
| Databáze: | OpenAIRE |
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