J 2022

Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller

LORIN, Valerie, Ignacio FERNANDEZ, Guillemette MASSE-RANSON, Melanie BOUVIN-PLEY, Luis M MOLINOS-ALBERT et. al.

Basic information

Original name

Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller

Authors

LORIN, Valerie, Ignacio FERNANDEZ, Guillemette MASSE-RANSON, Melanie BOUVIN-PLEY, Luis M MOLINOS-ALBERT, Cyril PLANCHAIS, Thierry HIEU, Gerard PEHAU-ARNAUDET, Dominik HREBÍK (703 Slovakia, belonging to the institution), Giulia GIRELLI-ZUBANI, Oriane FIQUET, Florence GUIVEL-BENHASSINE, Rogier W SANDERS, Bruce D WALKER, Olivier SCHWARTZ, Johannes F SCHEID, Jordan D DIMITROV, Pavel PLEVKA (203 Czech Republic, guarantor, belonging to the institution), Martine BRAIBANT, Michael S SEAMAN, Francois BONTEMS, James p DI SANTO, Felix A REY and Hugo MOUQUET

Edition

JOURNAL OF EXPERIMENTAL MEDICINE, UNITED STATES, ROCKEFELLER UNIV PRESS, 2022, 0022-1007

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30102 Immunology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 15.300

RIV identification code

RIV/00216224:14740/22:00127891

Organization unit

Central European Institute of Technology

UT WoS

000867703500001

Keywords in English

B-CELLSSTANDARDIZED ASSESSMENTSENVELOPE GLYCOPROTEINEFFICIENT GENERATIONMONOCLONAL-ANTIBODYCRYSTAL-STRUCTUREPOTENTGLYCANGP120MATURATION

Tags

Tags

International impact, Reviewed
Změněno: 11/1/2023 15:45, Mgr. Pavla Foltynová, Ph.D.

Abstract

V originále

Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG(+) or IgA(+) blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-angstrom resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers.