Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses.

Abstract:

:Antibodies capable of neutralizing divergent influenza A viruses could form the basis of a universal vaccine. Here, from subjects enrolled in an H5N1 DNA/MIV-prime-boost influenza vaccine trial, we sorted hemagglutinin cross-reactive memory B cells and identified three antibody classes, each capable of neutralizing diverse subtypes of group 1 and group 2 influenza A viruses. Co-crystal structures with hemagglutinin revealed that each class utilized characteristic germline genes and convergent sequence motifs to recognize overlapping epitopes in the hemagglutinin stem. All six analyzed subjects had sequences from at least one multidonor class, and-in half the subjects-multidonor-class sequences were recovered from >40% of cross-reactive B cells. By contrast, these multidonor-class sequences were rare in published antibody datasets. Vaccination with a divergent hemagglutinin can thus increase the frequency of B cells encoding broad influenza A-neutralizing antibodies. We propose the sequence signature-quantified prevalence of these B cells as a metric to guide universal influenza A immunization strategies.

journal_name

Cell

journal_title

Cell

authors

Joyce MG,Wheatley AK,Thomas PV,Chuang GY,Soto C,Bailer RT,Druz A,Georgiev IS,Gillespie RA,Kanekiyo M,Kong WP,Leung K,Narpala SN,Prabhakaran MS,Yang ES,Zhang B,Zhang Y,Asokan M,Boyington JC,Bylund T,Darko S,Lees

doi

10.1016/j.cell.2016.06.043

subject

Has Abstract

pub_date

2016-07-28 00:00:00

pages

609-623

issue

3

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(16)30851-0

journal_volume

166

pub_type

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