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

Todd Bradley; Justin Pollara; Sampa Santra; Nathan Vandergrift; Srivamshi Pittala; Chris Bailey-Kellogg; Xiaoying Shen; Robert Parks; Derrick Goodman; Amanda Eaton; Harikrishnan Balachandran; 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

doi:10.1038/ncomms15711

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

Todd Bradley, Justin Pollara, Sampa Santra, Nathan Vandergrift, Srivamshi Pittala, Chris Bailey-Kellogg, Xiaoying Shen, Robert Parks, Derrick Goodman, Amanda Eaton, Harikrishnan Balachandran, Linh V. MacH, Kevin O. Saunders, Joshua A. Weiner, Richard Scearce, Laura L. Sutherland, Sanjay Phogat, Jim Tartaglia, Steven G. Reed, Shiu Lok HuJames 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

106 Scopus citations

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.

Original language	English
Article number	15711
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/ncomms15711
State	Published - 8 Jun 2017
Externally published	Yes

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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, Article 15711. https://doi.org/10.1038/ncomms15711

@article{2672dd23da9c44a4ae4e7b1b89845c58,

title = "Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge",

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.",

author = "Todd Bradley and Justin Pollara and Sampa Santra and Nathan Vandergrift and Srivamshi Pittala and Chris Bailey-Kellogg and Xiaoying Shen and Robert Parks and Derrick Goodman and Amanda Eaton and Harikrishnan Balachandran and MacH, {Linh V.} and Saunders, {Kevin O.} and Weiner, {Joshua A.} and Richard Scearce and Sutherland, {Laura L.} and Sanjay Phogat and Jim Tartaglia and Reed, {Steven G.} and Hu, {Shiu Lok} and Theis, {James F.} and Abraham Pinter and Montefiori, {David C.} and Kepler, {Thomas B.} and Peachman, {Kristina K.} and Mangala Rao and Michael, {Nelson L.} and Suscovich, {Todd J.} and Galit Alter and Ackerman, {Margaret E.} and Moody, {M. Anthony} and Liao, {Hua Xin} and Georgia Tomaras and Guido Ferrari and Korber, {Bette T.} and Haynes, {Barton F.}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2017.",

year = "2017",

month = jun,

day = "8",

doi = "10.1038/ncomms15711",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

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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, SL, Theis, JF, Pinter, A, Montefiori, DC, Kepler, TB, Peachman, KK, Rao, M, Michael, NL, Suscovich, TJ, Alter, G, Ackerman, ME, Moody, MA, Liao, HX, Tomaras, G, Ferrari, G, Korber, BT & Haynes, BF 2017, 'Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge', Nature Communications, vol. 8, 15711. https://doi.org/10.1038/ncomms15711

TY - JOUR

T1 - Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge

AU - Bradley, Todd

AU - Pollara, Justin

AU - Santra, Sampa

AU - Vandergrift, Nathan

AU - Pittala, Srivamshi

AU - Bailey-Kellogg, Chris

AU - Shen, Xiaoying

AU - Parks, Robert

AU - Goodman, Derrick

AU - Eaton, Amanda

AU - Balachandran, Harikrishnan

AU - MacH, Linh V.

AU - Saunders, Kevin O.

AU - Weiner, Joshua A.

AU - Scearce, Richard

AU - Sutherland, Laura L.

AU - Phogat, Sanjay

AU - Tartaglia, Jim

AU - Reed, Steven G.

AU - Hu, Shiu Lok

AU - Theis, James F.

AU - Pinter, Abraham

AU - Montefiori, David C.

AU - Kepler, Thomas B.

AU - Peachman, Kristina K.

AU - Rao, Mangala

AU - Michael, Nelson L.

AU - Suscovich, Todd J.

AU - Alter, Galit

AU - Ackerman, Margaret E.

AU - Moody, M. Anthony

AU - Liao, Hua Xin

AU - Tomaras, Georgia

AU - Ferrari, Guido

AU - Korber, Bette T.

AU - Haynes, Barton F.

PY - 2017/6/8

Y1 - 2017/6/8

N2 - 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.

AB - 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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U2 - 10.1038/ncomms15711

DO - 10.1038/ncomms15711

M3 - Article

C2 - 28593989

AN - SCOPUS:85020430149

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 15711

ER -

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

Abstract

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