Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses.


Journal

The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R

Informations de publication

Date de publication:
07 10 2019
Historique:
received: 12 04 2019
revised: 29 05 2019
accepted: 24 06 2019
pubmed: 28 7 2019
medline: 11 6 2020
entrez: 27 7 2019
Statut: ppublish

Résumé

Human anti-HIV-1 broadly neutralizing antibodies (bNAbs) protect against infection in animal models. However, bNAbs have not been elicited by vaccination in diverse wild-type animals or humans, in part because B cells expressing the precursors of these antibodies do not recognize most HIV-1 envelopes (Envs). Immunogens have been designed that activate these B cell precursors in vivo, but they also activate competing off-target responses. Here we report on a complementary approach to expand specific B cells using an anti-idiotypic antibody, iv8, that selects for naive human B cells expressing immunoglobulin light chains with 5-amino acid complementarity determining region 3s, a key feature of anti-CD4 binding site (CD4bs)-specific VRC01-class antibodies. In mice, iv8 induced target cells to expand and mature in the context of a polyclonal immune system and produced serologic responses targeting the CD4bs on Env. In summary, the results demonstrate that an anti-idiotypic antibody can specifically recognize and expand rare B cells that express VRC01-class antibodies against HIV-1.

Identifiants

pubmed: 31345931
pii: jem.20190446
doi: 10.1084/jem.20190446
pmc: PMC6780999
doi:

Substances chimiques

Antibodies, Anti-Idiotypic 0
Antibodies, Neutralizing 0
HIV Antibodies 0
HIV Envelope Protein gp160 0

Banques de données

GENBANK
['MK611925', 'MK611928']
PDB
['6MFT']

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

2316-2330

Subventions

Organisme : NIAID NIH HHS
ID : P01 AI138212
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI081625
Pays : United States
Organisme : NIH HHS
ID : S10 OD021832
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI109632
Pays : United States

Informations de copyright

© 2019 Dosenovic et al.

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Auteurs

Pia Dosenovic (P)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

Anna-Klara Pettersson (AK)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

Abigail Wall (A)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Eddy S Thientosapol (ES)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

Junli Feng (J)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Connor Weidle (C)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Komal Bhullar (K)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

Ervin E Kara (EE)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

Harald Hartweger (H)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

Joy A Pai (JA)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY.

Matthew D Gray (MD)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

K Rachael Parks (KR)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
University of Washington University of Washington, Department of Global Health, Seattle, WA.

Justin J Taylor (JJ)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
University of Washington University of Washington, Department of Global Health, Seattle, WA.
University of Washington University of Washington, Department of Immunology, Seattle, WA.

Marie Pancera (M)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Leonidas Stamatatos (L)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA lstamata@fredhutch.org.
University of Washington University of Washington, Department of Global Health, Seattle, WA.

Michel C Nussenzweig (MC)

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY nussen@mail.rockefeller.edu.
Howard Hughes Medical Institute, Chevy Chase, MD.

Andrew T McGuire (AT)

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA amcguire@fredhutch.org.
University of Washington University of Washington, Department of Global Health, Seattle, WA.

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Classifications MeSH