Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge.
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.
Bradley, T; Pollara, J; Santra, S; Vandergrift, N; Pittala, S; Bailey-Kellogg, C; Shen, X; Parks, R; Goodman, D; Eaton, A; Balachandran, H; Mach, LV; Saunders, KO; Weiner, JA; Scearce, R; Sutherland, LL; Phogat, S; Tartaglia, J; Reed, SG; Hu, S-L; Theis, JF; Pinter, A; Montefiori, DC; Kepler, TB; Peachman, KK; Rao, M; Michael, NL; Suscovich, TJ; Alter, G; Ackerman, ME; Moody, MA; Liao, H-X; Tomaras, G; Ferrari, G; Korber, BT; Haynes, BF
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