Open AccessPentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge
Author(s) -
Todd Bradley,
Justin Pollara,
Sampa Santra,
Nathan Vandergrift,
Srivamshi Pittala,
Chris BaileyKellogg,
Xiaoying Shen,
Robert Parks,
Derrick Goodman,
Amanda Eaton,
Harikrishnan Balachandran,
Linh Mach,
Kevin O. Saunders,
Joshua A. Weiner,
Richard M. 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 D. Tomaras,
Guido Ferrari,
Bette T. Korber,
Barton F. Haynes
Publication year - 2017
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms15711
Subject(s) - virology , simian immunodeficiency virus , immunogen , antibody dependent cell mediated cytotoxicity , aids vaccines , hiv vaccine , antibody , vaccine trial , immunology , modified vaccinia ankara , biology , immunization , virus , vaccinia , recombinant dna , monoclonal antibody , biochemistry , gene
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.