Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120

Allan C. DeCamp; Morgane Rolland; Paul T. Edlefsen; Eric Sanders-Buell; Breana Hall; Craig A. Magaret; Andrew J. Fiore-Gartland; Michal Juraska; Lindsay N. Carpp; Shelly T. Karuna; Meera Bose; Steven LePore; Shana Miller; Annemarie O’Sullivan; Kultida Poltavee; Hongjun Bai; Kalpana Dommaraju; Hong Zhao; Kim Wong; Lennie Chen; Hasan Ahmed; Derrick Goodman; Matthew Z. Tay; Raphael Gottardo; Richard A. Koup; Robert Bailer; John R. Mascola; Barney S. Graham; Mario Roederer; Robert J. O’Connell; Nelson L. Michael; Merlin L. Robb; Elizabeth Adams; Patricia D’Souza; James Kublin; Lawrence Corey; Daniel E. Geraghty; Nicole Frahm; Georgia D. Tomaras; M. Juliana McElrath; Lisa Frenkel; Sheila Styrchak; Sodsai Tovanabutra; Magdalena E. Sobieszczyk; Scott M. Hammer; Jerome H. Kim; James I. Mullins; Peter B. Gilbert

doi:10.1371/journal.pone.0185959

Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120

Allan C. DeCamp^*, Morgane Rolland, Paul T. Edlefsen, Eric Sanders-Buell, Breana Hall, Craig A. Magaret, Andrew J. Fiore-Gartland, Michal Juraska, Lindsay N. Carpp, Shelly T. Karuna, Meera Bose, Steven LePore, Shana Miller, Annemarie O’Sullivan, Kultida Poltavee, Hongjun Bai, Kalpana Dommaraju, Hong Zhao, Kim Wong, Lennie ChenHasan Ahmed, Derrick Goodman, Matthew Z. Tay, Raphael Gottardo, Richard A. Koup, Robert Bailer, John R. Mascola, Barney S. Graham, Mario Roederer, Robert J. O’Connell, Nelson L. Michael, Merlin L. Robb, Elizabeth Adams, Patricia D’Souza, James Kublin, Lawrence Corey, Daniel E. Geraghty, Nicole Frahm, Georgia D. Tomaras, M. Juliana McElrath, Lisa Frenkel, Sheila Styrchak, Sodsai Tovanabutra, Magdalena E. Sobieszczyk, Scott M. Hammer, Jerome H. Kim, James I. Mullins, Peter B. Gilbert

^*Corresponding author for this work

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

28 Scopus citations

Abstract

Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P 0.04, Q-values 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

Original language	English
Article number	e0185959
Journal	PLoS ONE
Volume	12
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0185959
State	Published - Nov 2017
Externally published	Yes

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DeCamp, A. C., Rolland, M., Edlefsen, P. T., Sanders-Buell, E., Hall, B., Magaret, C. A., Fiore-Gartland, A. J., Juraska, M., Carpp, L. N., Karuna, S. T., Bose, M., LePore, S., Miller, S., O’Sullivan, A., Poltavee, K., Bai, H., Dommaraju, K., Zhao, H., Wong, K., ... Gilbert, P. B. (2017). Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120. PLoS ONE, 12(11), Article e0185959. https://doi.org/10.1371/journal.pone.0185959

@article{bc370c2bad78408e8548eef5bfa97a0f,

title = "Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120",

abstract = "Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P 0.04, Q-values 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.",

author = "DeCamp, {Allan C.} and Morgane Rolland and Edlefsen, {Paul T.} and Eric Sanders-Buell and Breana Hall and Magaret, {Craig A.} and Fiore-Gartland, {Andrew J.} and Michal Juraska and Carpp, {Lindsay N.} and Karuna, {Shelly T.} and Meera Bose and Steven LePore and Shana Miller and Annemarie O{\textquoteright}Sullivan and Kultida Poltavee and Hongjun Bai and Kalpana Dommaraju and Hong Zhao and Kim Wong and Lennie Chen and Hasan Ahmed and Derrick Goodman and Tay, {Matthew Z.} and Raphael Gottardo and Koup, {Richard A.} and Robert Bailer and Mascola, {John R.} and Graham, {Barney S.} and Mario Roederer and O{\textquoteright}Connell, {Robert J.} and Michael, {Nelson L.} and Robb, {Merlin L.} and Elizabeth Adams and Patricia D{\textquoteright}Souza and James Kublin and Lawrence Corey and Geraghty, {Daniel E.} and Nicole Frahm and Tomaras, {Georgia D.} and McElrath, {M. Juliana} and Lisa Frenkel and Sheila Styrchak and Sodsai Tovanabutra and Sobieszczyk, {Magdalena E.} and Hammer, {Scott M.} and Kim, {Jerome H.} and Mullins, {James I.} and Gilbert, {Peter B.}",

note = "Publisher Copyright: {\textcopyright} 2017, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.",

year = "2017",

month = nov,

doi = "10.1371/journal.pone.0185959",

language = "English",

volume = "12",

journal = "PLoS ONE",

issn = "1932-6203",

number = "11",

}

DeCamp, AC, Rolland, M, Edlefsen, PT, Sanders-Buell, E, Hall, B, Magaret, CA, Fiore-Gartland, AJ, Juraska, M, Carpp, LN, Karuna, ST, Bose, M, LePore, S, Miller, S, O’Sullivan, A, Poltavee, K, Bai, H, Dommaraju, K, Zhao, H, Wong, K, Chen, L, Ahmed, H, Goodman, D, Tay, MZ, Gottardo, R, Koup, RA, Bailer, R, Mascola, JR, Graham, BS, Roederer, M, O’Connell, RJ , Michael, NL, Robb, ML, Adams, E, D’Souza, P, Kublin, J, Corey, L, Geraghty, DE, Frahm, N, Tomaras, GD, McElrath, MJ, Frenkel, L, Styrchak, S, Tovanabutra, S, Sobieszczyk, ME, Hammer, SM, Kim, JH, Mullins, JI & Gilbert, PB 2017, 'Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120', PLoS ONE, vol. 12, no. 11, e0185959. https://doi.org/10.1371/journal.pone.0185959

TY - JOUR

T1 - Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120

AU - DeCamp, Allan C.

AU - Rolland, Morgane

AU - Edlefsen, Paul T.

AU - Sanders-Buell, Eric

AU - Hall, Breana

AU - Magaret, Craig A.

AU - Fiore-Gartland, Andrew J.

AU - Juraska, Michal

AU - Carpp, Lindsay N.

AU - Karuna, Shelly T.

AU - Bose, Meera

AU - LePore, Steven

AU - Miller, Shana

AU - O’Sullivan, Annemarie

AU - Poltavee, Kultida

AU - Bai, Hongjun

AU - Dommaraju, Kalpana

AU - Zhao, Hong

AU - Wong, Kim

AU - Chen, Lennie

AU - Ahmed, Hasan

AU - Goodman, Derrick

AU - Tay, Matthew Z.

AU - Gottardo, Raphael

AU - Koup, Richard A.

AU - Bailer, Robert

AU - Mascola, John R.

AU - Graham, Barney S.

AU - Roederer, Mario

AU - O’Connell, Robert J.

AU - Michael, Nelson L.

AU - Robb, Merlin L.

AU - Adams, Elizabeth

AU - D’Souza, Patricia

AU - Kublin, James

AU - Corey, Lawrence

AU - Geraghty, Daniel E.

AU - Frahm, Nicole

AU - Tomaras, Georgia D.

AU - McElrath, M. Juliana

AU - Frenkel, Lisa

AU - Styrchak, Sheila

AU - Tovanabutra, Sodsai

AU - Sobieszczyk, Magdalena E.

AU - Hammer, Scott M.

AU - Kim, Jerome H.

AU - Mullins, James I.

AU - Gilbert, Peter B.

N1 - Publisher Copyright: © 2017, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

PY - 2017/11

Y1 - 2017/11

N2 - Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P 0.04, Q-values 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

AB - Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P 0.04, Q-values 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

UR - http://www.scopus.com/inward/record.url?scp=85034248781&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0185959

DO - 10.1371/journal.pone.0185959

M3 - Article

C2 - 29149197

AN - SCOPUS:85034248781

SN - 1932-6203

VL - 12

JO - PLoS ONE

JF - PLoS ONE

IS - 11

M1 - e0185959

ER -

Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120

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