title: HIV-1 VACCINES. 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.
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. barton.haynes@duke.edu wilton.williams@duke.edu.
authors.forename: Wilton B
authors.initials: WB
authors.lastname: Williams
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Wiehe
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Trama
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Jones
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Hongshuo
authors.initials: H
authors.lastname: Song
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Dawn J
authors.initials: DJ
authors.lastname: Marshall
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Whitesides
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Kaitlin
authors.initials: K
authors.lastname: Sawatzki
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Axin
authors.initials: A
authors.lastname: Hua
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Pinghuang
authors.initials: P
authors.lastname: Liu
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Matthew Z
authors.initials: MZ
authors.lastname: Tay
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Seaton
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Foulger
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Krissey E
authors.initials: KE
authors.lastname: Lloyd
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Pollara
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Jae-Sung
authors.initials: JS
authors.lastname: Yu
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Vandergrift
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: Magdalena E
authors.initials: ME
authors.lastname: Sobieszczyk
authors.affiliation: Department of Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Hammer
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Shelly
authors.initials: S
authors.lastname: Karuna
authors.affiliation: The Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Gilbert
authors.affiliation: The Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Doug
authors.initials: D
authors.lastname: Grove
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Grunenberg
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.affiliation: The Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgan
authors.affiliation: The Aurum Institute, Johannesburg, South Africa.
authors.forename: Gavin
authors.initials: G
authors.lastname: Churchyard
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Janine
authors.initials: J
authors.lastname: Maenza
authors.affiliation: University of Rochester School of Medicine, Rochester, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Keefer
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.affiliation: Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA. barton.haynes@duke.edu wilton.williams@duke.edu.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D000917:Antibody Formation; D003429:Cross Reactions; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory; D007422:Intestines / Q000382:microbiology; D064307:Microbiota / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D019444:Vaccines, DNA