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Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge. 2017
Todd Bradley, and
Justin Pollara, and
Sampa Santra, and
Nathan Vandergrift, and
Srivamshi Pittala, and
Chris Bailey-Kellogg, and
Xiaoying Shen, and
Robert Parks, and
Derrick Goodman, and
Amanda Eaton, and
Harikrishnan Balachandran, and
Linh V Mach, and
Kevin O Saunders, and
Joshua A Weiner, and
Richard Scearce, and
Laura L Sutherland, and
Sanjay Phogat, and
Jim Tartaglia, and
Steven G Reed, and
Shiu-Lok Hu, and
James F Theis, and
Abraham Pinter, and
David C Montefiori, and
Thomas B Kepler, and
Kristina K Peachman, and
Mangala Rao, and
Nelson L Michael, and
Todd J Suscovich, and
Galit Alter, and
Margaret E Ackerman, and
M Anthony Moody, and
Hua-Xin Liao, and
Georgia Tomaras, and
Guido Ferrari, and
Bette T Korber, and
Barton F Haynes
Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
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.
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