Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge
| Autor: | Linh Mach, Bette T. Korber, Robert Parks, Hua-Xin Liao, Steven G. Reed, Barton F. Haynes, Amanda Eaton, Georgia D. Tomaras, Richard M. Scearce, Nelson L. Michael, Xiaoying Shen, James F. Theis, Galit Alter, M. Anthony Moody, Kristina K. Peachman, Srivamshi Pittala, Shiu Lok Hu, Guido Ferrari, David C. Montefiori, Harikrishnan Balachandran, Mangala Rao, Sanjay Phogat, Derrick Goodman, Thomas B. Kepler, Laura L. Sutherland, Margaret E. Ackerman, Todd Bradley, Joshua A. Weiner, Kevin O. Saunders, Justin Pollara, Sampa Santra, Jim Tartaglia, Nathan Vandergrift, Abraham Pinter, Todd J. Suscovich, Chris Bailey-Kellogg |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Immunogen viruses General Physics and Astronomy HIV Antibodies HIV Envelope Protein gp120 Serology law.invention Epitopes 0302 clinical medicine law Medicine Phylogeny Antibody-dependent cell-mediated cytotoxicity AIDS Vaccines Multidisciplinary biology virus diseases Recombinant Proteins 3. Good health Killer Cells Natural 030220 oncology & carcinogenesis Recombinant DNA Regression Analysis Female Simian Immunodeficiency Virus Antibody Protein Binding Science General Biochemistry Genetics and Molecular Biology Article Pentavalent vaccine 03 medical and health sciences Phagocytosis Neutralization Tests Predictive Value of Tests Animals Humans business.industry General Chemistry Complement System Proteins Vaccine efficacy Virology Macaca mulatta 030104 developmental biology Immunization Immunology Mutation biology.protein HIV-1 Leukocytes Mononuclear business |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-15 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 motifs in the immunogen to elicit a broader antibody response and enhance protection. We find that immunization of rhesus macaques with the pentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques from simian–human immunodeficiency virus (SHIV) challenge. Systems serology of the antibody responses identifies plasma antibody binding to HIV-infected cells, peak ADCC antibody titres, NK cell-mediated ADCC and antibody-mediated activation of MIP-1β in NK cells as the four immunological parameters that best predict decreased infection risk that are improved by the pentavalent vaccine. Thus inclusion of additional gp120 immunogens to a pox-prime/protein boost regimen can augment antibody responses and enhance protection from a SHIV challenge in rhesus macaques. A previous human HIV-1 vaccine clinical trial, boosting with HIV envelope protein from two strains, demonstrated moderate vaccine efficacy. Here, Bradley et al. show that a pentavalent HIV envelope protein boost improves protection from viral challenge in non-human primates and they identify immune correlates of protection. |
| Databáze: | OpenAIRE |
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