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

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 CR, Ransier A, Shen CH, Wang L, Whittle JR, Wu X, Yassine HM, Santos C, Matsuoka Y, Tsybovsky Y, Baxa U, NISC Comparative Sequencing Program, Mullikin JC, Subbarao K, Douek DC, Graham BS, Koup RA, Ledgerwood JE, Roederer M, Shapiro L, Kwong PD, Mascola JR, McDermott AB
Cell. 2016 166 (3): 609-623

PMID: 27453470 · PMCID: PMC4978566 · DOI:10.1016/j.cell.2016.06.043

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.

Published by Elsevier Inc.

MeSH Terms (19)

Adult Amino Acid Sequence Antibodies, Neutralizing Antibodies, Viral B-Lymphocytes Epitopes, B-Lymphocyte Female Gene Rearrangement, B-Lymphocyte, Heavy Chain Humans Immunologic Memory Influenza A virus Influenza A Virus, H5N1 Subtype Influenza Vaccines Male Middle Aged Models, Molecular Protein Structure, Tertiary Structure-Activity Relationship Young Adult

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