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 Hu, James 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 and Barton F. Haynes ()
Additional contact information
Todd Bradley: Duke Human Vaccine Institute, Duke University Medical Center
Justin Pollara: Duke Human Vaccine Institute, Duke University Medical Center
Sampa Santra: Beth Israel Deaconess Medical Center, Harvard Medical School
Nathan Vandergrift: Duke Human Vaccine Institute, Duke University Medical Center
Srivamshi Pittala: Dartmouth College
Chris Bailey-Kellogg: Dartmouth College
Xiaoying Shen: Duke Human Vaccine Institute, Duke University Medical Center
Robert Parks: Duke Human Vaccine Institute, Duke University Medical Center
Derrick Goodman: Duke Human Vaccine Institute, Duke University Medical Center
Amanda Eaton: Duke Human Vaccine Institute, Duke University Medical Center
Harikrishnan Balachandran: Beth Israel Deaconess Medical Center, Harvard Medical School
Linh V. Mach: Beth Israel Deaconess Medical Center, Harvard Medical School
Kevin O. Saunders: Duke Human Vaccine Institute, Duke University Medical Center
Joshua A. Weiner: Dartmouth College
Richard Scearce: Duke Human Vaccine Institute, Duke University Medical Center
Laura L. Sutherland: Duke Human Vaccine Institute, Duke University Medical Center
Sanjay Phogat: Sanofi Pasteur
Jim Tartaglia: Sanofi Pasteur
Steven G. Reed: Infectious Disease Research Institute
Shiu-Lok Hu: University of Washington
James F. Theis: Public Health Research Institute, New Jersey Medical School, Rutgers University
Abraham Pinter: Public Health Research Institute, New Jersey Medical School, Rutgers University
David C. Montefiori: Duke Human Vaccine Institute, Duke University Medical Center
Thomas B. Kepler: Boston University
Kristina K. Peachman: US Military HIV Research Program, Walter Reed Army Institute of Research
Mangala Rao: US Military HIV Research Program, Walter Reed Army Institute of Research
Nelson L. Michael: US Military HIV Research Program, Walter Reed Army Institute of Research
Todd J. Suscovich: Ragon Institute of MGH, MIT, and Harvard
Galit Alter: Ragon Institute of MGH, MIT, and Harvard
Margaret E. Ackerman: Dartmouth College
M. Anthony Moody: Duke Human Vaccine Institute, Duke University Medical Center
Hua-Xin Liao: Duke Human Vaccine Institute, Duke University Medical Center
Georgia Tomaras: Duke Human Vaccine Institute, Duke University Medical Center
Guido Ferrari: Duke Human Vaccine Institute, Duke University Medical Center
Bette T. Korber: Los Alamos National Laboratories
Barton F. Haynes: Duke Human Vaccine Institute, Duke University Medical Center

Nature Communications, 2017, vol. 8, issue 1, 1-15

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15711

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