Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies

Wilton B. Williams, Hua Xin Liao, M. Anthony Moody, Thomas B. Kepler, S. Munir Alam, Feng Gao, Kevin Wiehe, Ashley M. Trama, Kathryn Jones, Ruijun Zhang, Hongshuo Song, Dawn J. Marshall, John F. Whitesides, Kaitlin Sawatzki, Axin Hua, Pinghuang Liu, Matthew Z. Tay, Kelly E. Seaton, Xiaoying Shen, Andrew FoulgerKrissey E. Lloyd, Robert Parks, Justin Pollara, Guido Ferrari, Jae Sung Yu, Nathan Vandergrift, David C. Montefiori, Magdalena E. Sobieszczyk, Scott Hammer, Shelly Karuna, Peter Gilbert, Doug Grove, Nicole Grunenberg, M. Juliana McElrath, John R. Mascola, Richard A. Koup, Lawrence Corey, Gary J. Nabel, Cecilia Morgan, Gavin Churchyard, Janine Maenza, Michael Keefer, Barney S. Graham, Lindsey R. Baden, Georgia D. Tomaras, Barton F. Haynes

Research output: Contribution to journalArticle

Abstract

An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than to gp120, and repertoire analysis demonstrated that 93% of HIV-1-reactive Abs from memory B cells responded to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies were non-neutralizing and frequently polyreactive with host and environmental antigens, including intestinal microbiota (IM). Next-generation sequencing of an immunoglobulin heavy chain variable region repertoire before vaccination revealed an Env-IM cross-reactive Ab that was clonally related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy.

Original languageEnglish (US)
Article numberaab1253
JournalScience
Volume349
Issue number6249
DOIs
StatePublished - Aug 14 2015
Externally publishedYes

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AIDS Vaccines
Microbiota
HIV-1
Immunity
Antibodies
Vaccines
Antibody Formation
Adenovirus Vaccines
Immunoglobulin Heavy Chains
Synthetic Vaccines
DNA Vaccines
Adenoviridae
Vaccination
B-Lymphocytes
Monoclonal Antibodies
Antigens
DNA
Gastrointestinal Microbiome

ASJC Scopus subject areas

  • General

Cite this

Williams, W. B., Liao, H. X., Moody, M. A., Kepler, T. B., Alam, S. M., Gao, F., ... Haynes, B. F. (2015). Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science, 349(6249), [aab1253]. https://doi.org/10.1126/science.aab1253

Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. / Williams, Wilton B.; Liao, Hua Xin; Moody, M. Anthony; Kepler, Thomas B.; Alam, S. Munir; Gao, Feng; Wiehe, Kevin; Trama, Ashley M.; Jones, Kathryn; Zhang, Ruijun; Song, Hongshuo; Marshall, Dawn J.; Whitesides, John F.; Sawatzki, Kaitlin; Hua, Axin; Liu, Pinghuang; Tay, Matthew Z.; Seaton, Kelly E.; Shen, Xiaoying; Foulger, Andrew; Lloyd, Krissey E.; Parks, Robert; Pollara, Justin; Ferrari, Guido; Yu, Jae Sung; Vandergrift, Nathan; Montefiori, David C.; Sobieszczyk, Magdalena E.; Hammer, Scott; Karuna, Shelly; Gilbert, Peter; Grove, Doug; Grunenberg, Nicole; McElrath, M. Juliana; Mascola, John R.; Koup, Richard A.; Corey, Lawrence; Nabel, Gary J.; Morgan, Cecilia; Churchyard, Gavin; Maenza, Janine; Keefer, Michael; Graham, Barney S.; Baden, Lindsey R.; Tomaras, Georgia D.; Haynes, Barton F.

In: Science, Vol. 349, No. 6249, aab1253, 14.08.2015.

Research output: Contribution to journalArticle

Williams, WB, Liao, HX, Moody, MA, Kepler, TB, Alam, SM, Gao, F, Wiehe, K, Trama, AM, Jones, K, Zhang, R, Song, H, Marshall, DJ, Whitesides, JF, Sawatzki, K, Hua, A, Liu, P, Tay, MZ, Seaton, KE, Shen, X, Foulger, A, Lloyd, KE, Parks, R, Pollara, J, Ferrari, G, Yu, JS, Vandergrift, N, Montefiori, DC, Sobieszczyk, ME, Hammer, S, Karuna, S, Gilbert, P, Grove, D, Grunenberg, N, McElrath, MJ, Mascola, JR, Koup, RA, Corey, L, Nabel, GJ, Morgan, C, Churchyard, G, Maenza, J, Keefer, M, Graham, BS, Baden, LR, Tomaras, GD & Haynes, BF 2015, 'Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies', Science, vol. 349, no. 6249, aab1253. https://doi.org/10.1126/science.aab1253
Williams WB, Liao HX, Moody MA, Kepler TB, Alam SM, Gao F et al. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science. 2015 Aug 14;349(6249). aab1253. https://doi.org/10.1126/science.aab1253
Williams, Wilton B. ; Liao, Hua Xin ; Moody, M. Anthony ; Kepler, Thomas B. ; Alam, S. Munir ; Gao, Feng ; Wiehe, Kevin ; Trama, Ashley M. ; Jones, Kathryn ; Zhang, Ruijun ; Song, Hongshuo ; Marshall, Dawn J. ; Whitesides, John F. ; Sawatzki, Kaitlin ; Hua, Axin ; Liu, Pinghuang ; Tay, Matthew Z. ; Seaton, Kelly E. ; Shen, Xiaoying ; Foulger, Andrew ; Lloyd, Krissey E. ; Parks, Robert ; Pollara, Justin ; Ferrari, Guido ; Yu, Jae Sung ; Vandergrift, Nathan ; Montefiori, David C. ; Sobieszczyk, Magdalena E. ; Hammer, Scott ; Karuna, Shelly ; Gilbert, Peter ; Grove, Doug ; Grunenberg, Nicole ; McElrath, M. Juliana ; Mascola, John R. ; Koup, Richard A. ; Corey, Lawrence ; Nabel, Gary J. ; Morgan, Cecilia ; Churchyard, Gavin ; Maenza, Janine ; Keefer, Michael ; Graham, Barney S. ; Baden, Lindsey R. ; Tomaras, Georgia D. ; Haynes, Barton F. / Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. In: Science. 2015 ; Vol. 349, No. 6249.
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title = "Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies",
abstract = "An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than to gp120, and repertoire analysis demonstrated that 93{\%} of HIV-1-reactive Abs from memory B cells responded to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies were non-neutralizing and frequently polyreactive with host and environmental antigens, including intestinal microbiota (IM). Next-generation sequencing of an immunoglobulin heavy chain variable region repertoire before vaccination revealed an Env-IM cross-reactive Ab that was clonally related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy.",
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T1 - Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies

AU - Williams, Wilton B.

AU - Liao, Hua Xin

AU - Moody, M. Anthony

AU - Kepler, Thomas B.

AU - Alam, S. Munir

AU - Gao, Feng

AU - Wiehe, Kevin

AU - Trama, Ashley M.

AU - Jones, Kathryn

AU - Zhang, Ruijun

AU - Song, Hongshuo

AU - Marshall, Dawn J.

AU - Whitesides, John F.

AU - Sawatzki, Kaitlin

AU - Hua, Axin

AU - Liu, Pinghuang

AU - Tay, Matthew Z.

AU - Seaton, Kelly E.

AU - Shen, Xiaoying

AU - Foulger, Andrew

AU - Lloyd, Krissey E.

AU - Parks, Robert

AU - Pollara, Justin

AU - Ferrari, Guido

AU - Yu, Jae Sung

AU - Vandergrift, Nathan

AU - Montefiori, David C.

AU - Sobieszczyk, Magdalena E.

AU - Hammer, Scott

AU - Karuna, Shelly

AU - Gilbert, Peter

AU - Grove, Doug

AU - Grunenberg, Nicole

AU - McElrath, M. Juliana

AU - Mascola, John R.

AU - Koup, Richard A.

AU - Corey, Lawrence

AU - Nabel, Gary J.

AU - Morgan, Cecilia

AU - Churchyard, Gavin

AU - Maenza, Janine

AU - Keefer, Michael

AU - Graham, Barney S.

AU - Baden, Lindsey R.

AU - Tomaras, Georgia D.

AU - Haynes, Barton F.

PY - 2015/8/14

Y1 - 2015/8/14

N2 - An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than to gp120, and repertoire analysis demonstrated that 93% of HIV-1-reactive Abs from memory B cells responded to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies were non-neutralizing and frequently polyreactive with host and environmental antigens, including intestinal microbiota (IM). Next-generation sequencing of an immunoglobulin heavy chain variable region repertoire before vaccination revealed an Env-IM cross-reactive Ab that was clonally related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy.

AB - An HIV-1 DNA prime vaccine, with a recombinant adenovirus type 5 (rAd5) boost, failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than to gp120, and repertoire analysis demonstrated that 93% of HIV-1-reactive Abs from memory B cells responded to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies were non-neutralizing and frequently polyreactive with host and environmental antigens, including intestinal microbiota (IM). Next-generation sequencing of an immunoglobulin heavy chain variable region repertoire before vaccination revealed an Env-IM cross-reactive Ab that was clonally related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy.

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