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
Celljournal_title
Cellauthors
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,Leesdoi
10.1016/j.cell.2016.06.043subject
Has Abstractpub_date
2016-07-28 00:00:00pages
609-623issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(16)30851-0journal_volume
166pub_type
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