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

• DOI: 10.1038/ncomms15711
• Publication Date: 2017-06-08T11:18:59Z
• Authors: Todd Bradley; Justin Pollara; Sampa Santra; Nathan Vandergrift; Srivamshi Pittala; Chris Bailey-Kellogg; Xiaoying Shen; Robert Parks; Derrick Goodman; Amanda Eaton; Harikrishnan Bala...; 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; Barton F. Haynes
• Keywords: Male; Science; HIV Antibodies; HIV Envelope Protein gp120; Article; Epitopes; 03 medical and health sciences; 0302 clinical medicine; Phagocytosis; Neutralization Tests; Predictive Value of Tests; 616; Animals; Humans; Phylogeny; AIDS Vaccines; Q; Complement System Proteins; Macaca mulatta; Recombinant Proteins; 3. Good health; Killer Cells, Natural; Mutation; HIV-1; Leukocytes, Mononuclear; Female; Protein Binding

AbstractThe 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.