Bradley, ToddPollara, JustinSantra, SampaVandergrift, NathanPittala, SrivamshiBailey-Kellogg, ChrisShen, XiaoyingParks, RobertGoodman, DerrickEaton, AmandaBalachandran, HarikrishnanMach, Linh V.Saunders, Kevin O.Weiner, Joshua A.Scearce, RichardSutherland, Laura L.Phogat, SanjayTartaglia, JimReed, Steven G.Hu, Shiu-LokTheis, James F.Pinter, AbrahamMontefiori, David C.Kepler, Thomas B.Peachman, Kristina K.Rao, MangalaMichael, Nelson L.Suscovich, Todd J.Alter, GalitAckerman, Margaret E.Moody, M. AnthonyLiao, Hua-XinTomaras, GeorgiaFerrari, GuidoKorber, Bette T.Haynes, Barton F.2017-07-242017Bradley, T., J. Pollara, S. Santra, N. Vandergrift, S. Pittala, C. Bailey-Kellogg, X. Shen, et al. 2017. “Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge.” Nature Communications 8 (1): 15711. doi:10.1038/ncomms15711. http://dx.doi.org/10.1038/ncomms15711.http://nrs.harvard.edu/urn-3:HUL.InstRepos:33490757The 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.en-USJournal Article2017-07-2410.1038/ncomms15711