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 Foulger; Krissey 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

doi:10.1126/science.aab1253

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 journal › Article › peer-review

115 Scopus citations

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 language	English (US)
Article number	aab1253
Journal	Science
Volume	349
Issue number	6249
DOIs	https://doi.org/10.1126/science.aab1253
State	Published - Aug 14 2015
Externally published	Yes

ASJC Scopus subject areas

General

Access to Document

10.1126/science.aab1253

Cite this

Williams, W. B., Liao, H. X., Moody, M. A., Kepler, T. B., Alam, S. M., Gao, F., Wiehe, K., Trama, A. M., Jones, K., Zhang, R., Song, H., Marshall, D. J., Whitesides, J. F., Sawatzki, K., Hua, A., Liu, P., Tay, M. Z., Seaton, K. E., Shen, X., ... Haynes, B. F. (2015). Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science, 349(6249), Article aab1253. https://doi.org/10.1126/science.aab1253

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

@article{506244db9dde487a82c326e183dce27d,

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.",

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

year = "2015",

month = aug,

day = "14",

doi = "10.1126/science.aab1253",

language = "English (US)",

volume = "349",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6249",

}

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=84940192994&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940192994&partnerID=8YFLogxK

U2 - 10.1126/science.aab1253

DO - 10.1126/science.aab1253

M3 - Article

C2 - 26229114

AN - SCOPUS:84940192994

SN - 0036-8075

VL - 349

JO - Science

JF - Science

IS - 6249

M1 - aab1253

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this