Open AccessThe respiratory syncytial virus (RSV) prefusion F‐protein functional antibody repertoire in adult healthy donors
Author(s) -
Andreano Emanuele,
Paciello Ida,
Bardelli Monia,
Tavarini Simona,
Sammicheli Chiara,
Frigimelica Elisabetta,
Guidotti Silvia,
Torricelli Giulia,
Biancucci Marco,
D’Oro Ugo,
Chandramouli Sumana,
Bottomley Matthew J,
Rappuoli Rino,
Finco Oretta,
Buricchi Francesca
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202114035
Subject(s) - repertoire , medicine , library science , virology , history , art , computer science , literature
Respiratory syncytial virus (RSV) is the leading cause of death from lower respiratory tract infection in infants and children, and is responsible for considerable morbidity and mortality in older adults. Vaccines for pregnant women and elderly which are in phase III clinical studies target people with pre‐existing natural immunity against RSV. To investigate the background immunity which will be impacted by vaccination, we single cell‐sorted human memory B cells and dissected functional and genetic features of neutralizing antibodies (nAbs) induced by natural infection. Most nAbs recognized both the prefusion and postfusion conformations of the RSV F‐protein (cross‐binders) while a smaller fraction bound exclusively to the prefusion conformation. Cross‐binder nAbs used a wide array of gene rearrangements, while preF‐binder nAbs derived mostly from the expansion of B‐cell clonotypes from the IGHV1 germline. This latter class of nAbs recognizes an epitope located between Site Ø, Site II, and Site V on the F‐protein, identifying an important site of pathogen vulnerability.