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

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...

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Podrobná bibliografia
Vydané v:	Cell Ročník 166; číslo 3; s. 609
Hlavní autori:	Joyce, M Gordon, Wheatley, Adam K, Thomas, Paul V, Chuang, Gwo-Yu, Soto, Cinque, Bailer, Robert T, Druz, Aliaksandr, Georgiev, Ivelin S, Gillespie, Rebecca A, Kanekiyo, Masaru, Kong, Wing-Pui, Leung, Kwanyee, Narpala, Sandeep N, Prabhakaran, Madhu S, Yang, Eun Sung, Zhang, Baoshan, Zhang, Yi, Asokan, Mangaiarkarasi, Boyington, Jeffrey C, Bylund, Tatsiana, Darko, Sam, Lees, Christopher R, Ransier, Amy, Shen, Chen-Hsiang, Wang, Lingshu, Whittle, James R, Wu, Xueling, Yassine, Hadi M, Santos, Celia, Matsuoka, Yumiko, Tsybovsky, Yaroslav, Baxa, Ulrich, Mullikin, James C, Subbarao, Kanta, Douek, Daniel C, Graham, Barney S, Koup, Richard A, Ledgerwood, Julie E, Roederer, Mario, Shapiro, Lawrence, Kwong, Peter D, Mascola, John R, McDermott, Adrian B
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 28.07.2016
Predmet:	Adult Amino Acid Sequence Antibodies, Neutralizing - chemistry Antibodies, Neutralizing - genetics Antibodies, Neutralizing - immunology Antibodies, Viral - chemistry Antibodies, Viral - genetics Antibodies, Viral - immunology B-Lymphocytes - immunology Epitopes, B-Lymphocyte Female Gene Rearrangement, B-Lymphocyte, Heavy Chain Humans Immunologic Memory Influenza A virus - immunology Influenza A Virus, H5N1 Subtype - immunology Influenza Vaccines - immunology Male Middle Aged Models, Molecular Protein Structure, Tertiary Structure-Activity Relationship Young Adult
ISSN:	1097-4172, 1097-4172
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4172 1097-4172
DOI:	10.1016/j.cell.2016.06.043