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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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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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.
AbstractList	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.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. 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.
Author	Santos, Celia Douek, Daniel C Kwong, Peter D Yang, Eun Sung Zhang, Baoshan Lees, Christopher R Soto, Cinque Darko, Sam Matsuoka, Yumiko Mascola, John R Kong, Wing-Pui Zhang, Yi Joyce, M Gordon Mullikin, James C Graham, Barney S Roederer, Mario Shen, Chen-Hsiang Narpala, Sandeep N Wu, Xueling Asokan, Mangaiarkarasi Koup, Richard A Whittle, James R Druz, Aliaksandr Georgiev, Ivelin S Kanekiyo, Masaru Subbarao, Kanta Yassine, Hadi M Wang, Lingshu Ransier, Amy Tsybovsky, Yaroslav Chuang, Gwo-Yu Bailer, Robert T Baxa, Ulrich Thomas, Paul V Gillespie, Rebecca A Boyington, Jeffrey C Bylund, Tatsiana Ledgerwood, Julie E Leung, Kwanyee McDermott, Adrian B Wheatley, Adam K Shapiro, Lawrence Prabhakaran, Madhu S
AuthorAffiliation	NIH Intramural Sequencing Center (NISC), National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
AuthorAffiliation_xml	– name: NIH Intramural Sequencing Center (NISC), National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Author_xml	– sequence: 1 givenname: M Gordon surname: Joyce fullname: Joyce, M Gordon organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 2 givenname: Adam K surname: Wheatley fullname: Wheatley, Adam K organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 3 givenname: Paul V surname: Thomas fullname: Thomas, Paul V organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 4 givenname: Gwo-Yu surname: Chuang fullname: Chuang, Gwo-Yu organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 5 givenname: Cinque surname: Soto fullname: Soto, Cinque organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 6 givenname: Robert T surname: Bailer fullname: Bailer, Robert T organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 7 givenname: Aliaksandr surname: Druz fullname: Druz, Aliaksandr organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 8 givenname: Ivelin S surname: Georgiev fullname: Georgiev, Ivelin S organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Pathology, Microbiology, and Immunology and Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN 37232, USA – sequence: 9 givenname: Rebecca A surname: Gillespie fullname: Gillespie, Rebecca A organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 10 givenname: Masaru surname: Kanekiyo fullname: Kanekiyo, Masaru organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 11 givenname: Wing-Pui surname: Kong fullname: Kong, Wing-Pui organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 12 givenname: Kwanyee surname: Leung fullname: Leung, Kwanyee organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 13 givenname: Sandeep N surname: Narpala fullname: Narpala, Sandeep N organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 14 givenname: Madhu S surname: Prabhakaran fullname: Prabhakaran, Madhu S organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 15 givenname: Eun Sung surname: Yang fullname: Yang, Eun Sung organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 16 givenname: Baoshan surname: Zhang fullname: Zhang, Baoshan organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 17 givenname: Yi surname: Zhang fullname: Zhang, Yi organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 18 givenname: Mangaiarkarasi surname: Asokan fullname: Asokan, Mangaiarkarasi organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 19 givenname: Jeffrey C surname: Boyington fullname: Boyington, Jeffrey C organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 20 givenname: Tatsiana surname: Bylund fullname: Bylund, Tatsiana organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 21 givenname: Sam surname: Darko fullname: Darko, Sam organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 22 givenname: Christopher R surname: Lees fullname: Lees, Christopher R organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 23 givenname: Amy surname: Ransier fullname: Ransier, Amy organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 24 givenname: Chen-Hsiang surname: Shen fullname: Shen, Chen-Hsiang organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 25 givenname: Lingshu surname: Wang fullname: Wang, Lingshu organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 26 givenname: James R surname: Whittle fullname: Whittle, James R organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 27 givenname: Xueling surname: Wu fullname: Wu, Xueling organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 28 givenname: Hadi M surname: Yassine fullname: Yassine, Hadi M organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 29 givenname: Celia surname: Santos fullname: Santos, Celia organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 30 givenname: Yumiko surname: Matsuoka fullname: Matsuoka, Yumiko organization: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 31 givenname: Yaroslav surname: Tsybovsky fullname: Tsybovsky, Yaroslav organization: Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA – sequence: 32 givenname: Ulrich surname: Baxa fullname: Baxa, Ulrich organization: Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA – sequence: 33 givenname: James C surname: Mullikin fullname: Mullikin, James C organization: NIH Intramural Sequencing Center (NISC), National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 34 givenname: Kanta surname: Subbarao fullname: Subbarao, Kanta organization: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 35 givenname: Daniel C surname: Douek fullname: Douek, Daniel C organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 36 givenname: Barney S surname: Graham fullname: Graham, Barney S organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 37 givenname: Richard A surname: Koup fullname: Koup, Richard A organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 38 givenname: Julie E surname: Ledgerwood fullname: Ledgerwood, Julie E organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 39 givenname: Mario surname: Roederer fullname: Roederer, Mario organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA – sequence: 40 givenname: Lawrence surname: Shapiro fullname: Shapiro, Lawrence organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry & Molecular Biophysics and Department of Systems Biology, Columbia University, New York, NY 10027, USA – sequence: 41 givenname: Peter D surname: Kwong fullname: Kwong, Peter D email: pdkwong@nih.gov organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: pdkwong@nih.gov – sequence: 42 givenname: John R surname: Mascola fullname: Mascola, John R email: jmascola@nih.gov organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jmascola@nih.gov – sequence: 43 givenname: Adrian B surname: McDermott fullname: McDermott, Adrian B email: adrian.mcdermott@nih.gov organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: adrian.mcdermott@nih.gov
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/27453470$$D View this record in MEDLINE/PubMed
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References	27471961 - Cell. 2016 Jul 28;166(3):532-533. doi: 10.1016/j.cell.2016.07.023.
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SubjectTerms	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
Title	Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses
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