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

Todd Bradley, Justin Pollara, Sampa Santra, Nathan Vandergrift, Srivamshi Pittala, Chris Bailey-Kellogg, Xiaoying Shen, Robert Parks, Derrick Goodman, Amanda Eaton, Harikrishnan Balachandran, Linh V. MacH, Kevin O. Saunders, Joshua A. Weiner, Richard Scearce, Laura L. Sutherland, Sanjay Phogat, Jim Tartaglia, Steven G. Reed, Shiu Lok HuJames F. Theis, Abraham Pinter, David C. Montefiori, Thomas B. Kepler, Kristina K. Peachman, Mangala Rao, Nelson L. Michael, Todd J. Suscovich, Galit Alter, Margaret E. Ackerman, M. Anthony Moody, Hua Xin Liao, Georgia Tomaras, Guido Ferrari, Bette T. Korber, Barton F. Haynes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

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.

Original languageEnglish
Article number15711
JournalNature Communications
Volume8
DOIs
StatePublished - 8 Jun 2017
Externally publishedYes

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