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

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

in Adenoviridae / AIDS Vaccines - immunology / Antibodies, Monoclonal - genetics / Antibodies, Monoclonal - immunology / Antibody Formation / Cross Reactions / HIV Antibodies - genetics / HIV Antibodies - immunology / HIV Envelope Protein gp120 - immunology / HIV Envelope Protein gp41 - genetics / HIV Envelope Protein gp41 - immunology / HIV-1 - immunology / Humans / Immunity / Immunoglobulin Heavy Chains - genetics / Immunoglobulin Heavy Chains - immunology / Immunoglobulin Variable Region - genetics / Immunoglobulin Variable Region - immunology / Immunologic Memory / Intestines - microbiology / Microbiota - immunology / Vaccines, DNA - immunology

2015

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2015

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

2015

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Journal Article

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

Shen, Xiaoying,

Foulger, Andrew,

Grove, Doug,

Parks, Robert,

Baden, Lindsey R,

Williams, Wilton B,

Song, Hongshuo,

Haynes, Barton F,

Ferrari, Guido,

Mascola, John R,

Karuna, Shelly,

Sobieszczyk, Magdalena E,

Liu, Pinghuang,

Graham, Barney S,

Pollara, Justin,

Trama, Ashley M,

McElrath, M Juliana,

Tay, Matthew Z,

Gilbert, Peter,

Moody, M Anthony,

Zhang, Ruijun,

Hua, Axin,

Koup, Richard A,

Liao, Hua-Xin,

Gao, Feng,

Jones, Kathryn,

Morgan, Cecilia,

Corey, Lawrence,

Keefer, Michael,

Marshall, Dawn J,

Kepler, Thomas B,

Nabel, Gary J,

Hammer, Scott,

Grunenberg, Nicole,

Yu, Jae-Sung,

Maenza, Janine,

Whitesides, John F,

Churchyard, Gavin,

Seaton, Kelly E,

Lloyd, Krissey E,

Alam, S Munir,

Tomaras, Georgia D,

Wiehe, Kevin,

Montefiori, David C,

Sawatzki, Kaitlin,

Vandergrift, Nathan

2015

Overview

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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Subject

Adenoviridae

/ AIDS Vaccines - immunology

/ Antibodies, Monoclonal - genetics

/ Antibodies, Monoclonal - immunology

/ Antibody Formation

/ Cross Reactions

/ HIV Antibodies - genetics

/ HIV Antibodies - immunology

/ HIV Envelope Protein gp120 - immunology