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Nat Commun. 2017 Jun 8;8:15711. doi: 10.1038/ncomms15711.

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

Author information

1
Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
2
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
3
Dartmouth College, Hanover, New Hampshire 03755, USA.
4
Sanofi Pasteur, Swiftwater, Pennsylvania 18370, USA.
5
Infectious Disease Research Institute, Seattle, Washington 98109, USA.
6
Department of Pharmaceutics, University of Washington, Seattle, Washington 98195, USA.
7
Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey 07103, USA.
8
Department of Microbiology, Boston University, Boston, Massachusetts 02215, USA.
9
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
10
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland 20817, USA.
11
Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, USA.
12
Los Alamos National Laboratories, Los Alamos, New Mexico 87545, USA.

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.

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