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Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge
Bradley, T., Pollara, J., Santra, S., Vandergrift, N., Pittala, S., Bailey-Kellogg, C., Shen, X., Parks, R., Goodman, D., Eaton, A., Balachandran, H., Mach, L. V., Saunders, K. O., Weiner, J. A., Scearce, R., Sutherland, L. L., Phogat, S., Tartaglia, J., Reed, S. G., ... Haynes, B. F. (2017). Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge. Nature Communications, 8, 15711. Article 15711. https://doi.org/10.1038/ncomms15711
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.
