Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge

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 an...

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Vydáno v:Nature communications Ročník 8; číslo 1; s. 15711 - 15
Hlavní autoři: Bradley, Todd, Pollara, Justin, Santra, Sampa, Vandergrift, Nathan, Pittala, Srivamshi, Bailey-Kellogg, Chris, Shen, Xiaoying, Parks, Robert, Goodman, Derrick, Eaton, Amanda, Balachandran, Harikrishnan, Mach, Linh V., Saunders, Kevin O., Weiner, Joshua A., Scearce, Richard, Sutherland, Laura L., Phogat, Sanjay, Tartaglia, Jim, Reed, Steven G., Hu, Shiu-Lok, Theis, James F., Pinter, Abraham, Montefiori, David C., Kepler, Thomas B., Peachman, Kristina K., Rao, Mangala, Michael, Nelson L., Suscovich, Todd J., Alter, Galit, Ackerman, Margaret E., Moody, M. Anthony, Liao, Hua-Xin, Tomaras, Georgia, Ferrari, Guido, Korber, Bette T., Haynes, Barton F.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 08.06.2017
Nature Publishing Group
Nature Portfolio
Témata:
45/77
631/250/255/1901
631/250/590
692/308/2778
82/1
82/47
82/80
Acquired immune deficiency syndrome
AIDS
Antibodies
Health risks
HIV
Human immunodeficiency virus
Humanities and Social Sciences
Immunization
Infections
multidisciplinary
Proteins
Science
Science (multidisciplinary)
Vaccines
Viruses
Thailand
United States > US
Maryland
Massachusetts
New Jersey
ISSN:2041-1723, 2041-1723
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Shrnutí: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.
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ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms15711