Frequent Use of the IgA Isotype in Human B Cells Encoding Potent Norovirus-Specific Monoclonal Antibodies That Block HBGA Binding
Noroviruses (NoV) are the most common cause of non-bacterial acute gastroenteritis and cause local outbreaks of illness, especially in confined situations. Despite being identified four decades ago, the correlates of protection against norovirus gastroenteritis are still being elucidated. Recent stu...
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| Veröffentlicht in: | PLoS pathogens 2016-06, Vol.12 (6), p.e1005719-e1005719 |
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| description | Noroviruses (NoV) are the most common cause of non-bacterial acute gastroenteritis and cause local outbreaks of illness, especially in confined situations. Despite being identified four decades ago, the correlates of protection against norovirus gastroenteritis are still being elucidated. Recent studies have shown an association of protection with NoV-specific serum histo-blood group antigen-blocking antibody and with serum IgA in patients vaccinated with NoV VLPs. Here, we describe the isolation and characterization of human monoclonal IgG and IgA antibodies against a GI.I NoV, Norwalk virus (NV). A higher proportion of the IgA antibodies blocked NV VLP binding to glycans than did IgG antibodies. We generated isotype-switched variants of IgG and IgA antibodies to study the effects of the constant domain on blocking and binding activities. The IgA form of antibodies appears to be more potent than the IgG form in blocking norovirus binding to histo-blood group antigens. These studies suggest a unique role for IgA antibodies in protection from NoV infections by blocking attachment to cell receptors. |
| doi_str_mv | 10.1371/journal.ppat.1005719 |
| format | Article |
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Despite being identified four decades ago, the correlates of protection against norovirus gastroenteritis are still being elucidated. Recent studies have shown an association of protection with NoV-specific serum histo-blood group antigen-blocking antibody and with serum IgA in patients vaccinated with NoV VLPs. Here, we describe the isolation and characterization of human monoclonal IgG and IgA antibodies against a GI.I NoV, Norwalk virus (NV). A higher proportion of the IgA antibodies blocked NV VLP binding to glycans than did IgG antibodies. We generated isotype-switched variants of IgG and IgA antibodies to study the effects of the constant domain on blocking and binding activities. The IgA form of antibodies appears to be more potent than the IgG form in blocking norovirus binding to histo-blood group antigens. These studies suggest a unique role for IgA antibodies in protection from NoV infections by blocking attachment to cell receptors.</description><identifier>ISSN: 1553-7374</identifier><identifier>ISSN: 1553-7366</identifier><identifier>EISSN: 1553-7374</identifier><identifier>DOI: 10.1371/journal.ppat.1005719</identifier><identifier>PMID: 27355511</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antibodies, Monoclonal - immunology ; Antigens ; B cells ; B-Lymphocytes - immunology ; Biology and Life Sciences ; Blood Group Antigens - immunology ; Blood groups ; Blotting, Western ; Caliciviridae Infections - immunology ; Cell Line ; Chromatography ; Enzyme-Linked Immunosorbent Assay ; Epidemics ; Funding ; Gastroenteritis ; Gastroenteritis - immunology ; Genomes ; Health aspects ; Humans ; Hybridomas ; Immunoglobulin A ; Immunoglobulin A - immunology ; Immunoglobulin G - immunology ; Immunoglobulins ; Infections ; Inventors ; Medicine and Health Sciences ; Norovirus ; Norwalk virus ; Norwalk virus - immunology ; Polymerase Chain Reaction ; Prevention ; Proteins ; Research and Analysis Methods ; Studies ; Viruses</subject><ispartof>PLoS pathogens, 2016-06, Vol.12 (6), p.e1005719-e1005719</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Sapparapu G, Czakó R, Alvarado G, Shanker S, Prasad BVV, Atmar RL, et al. (2016) Frequent Use of the IgA Isotype in Human B Cells Encoding Potent Norovirus-Specific Monoclonal Antibodies That Block HBGA Binding. PLoS Pathog 12(6): e1005719. doi:10.1371/journal.ppat.1005719</rights><rights>2016 Sapparapu et al 2016 Sapparapu et al</rights><rights>2016 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Sapparapu G, Czakó R, Alvarado G, Shanker S, Prasad BVV, Atmar RL, et al. (2016) Frequent Use of the IgA Isotype in Human B Cells Encoding Potent Norovirus-Specific Monoclonal Antibodies That Block HBGA Binding. 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immunology</topic><topic>Antigens</topic><topic>B cells</topic><topic>B-Lymphocytes - immunology</topic><topic>Biology and Life Sciences</topic><topic>Blood Group Antigens - immunology</topic><topic>Blood groups</topic><topic>Blotting, Western</topic><topic>Caliciviridae Infections - immunology</topic><topic>Cell Line</topic><topic>Chromatography</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epidemics</topic><topic>Funding</topic><topic>Gastroenteritis</topic><topic>Gastroenteritis - immunology</topic><topic>Genomes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hybridomas</topic><topic>Immunoglobulin A</topic><topic>Immunoglobulin A - immunology</topic><topic>Immunoglobulin G - immunology</topic><topic>Immunoglobulins</topic><topic>Infections</topic><topic>Inventors</topic><topic>Medicine and Health Sciences</topic><topic>Norovirus</topic><topic>Norwalk virus</topic><topic>Norwalk virus - immunology</topic><topic>Polymerase Chain Reaction</topic><topic>Prevention</topic><topic>Proteins</topic><topic>Research and Analysis Methods</topic><topic>Studies</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sapparapu, Gopal</creatorcontrib><creatorcontrib>Czakó, Rita</creatorcontrib><creatorcontrib>Alvarado, Gabriela</creatorcontrib><creatorcontrib>Shanker, Sreejesh</creatorcontrib><creatorcontrib>Prasad, B V Venkataram</creatorcontrib><creatorcontrib>Atmar, Robert L</creatorcontrib><creatorcontrib>Estes, Mary K</creatorcontrib><creatorcontrib>Crowe, Jr, James E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS pathogens</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sapparapu, Gopal</au><au>Czakó, Rita</au><au>Alvarado, Gabriela</au><au>Shanker, Sreejesh</au><au>Prasad, B V Venkataram</au><au>Atmar, Robert L</au><au>Estes, Mary K</au><au>Crowe, Jr, James E</au><au>Wilson, Patrick C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Frequent Use of the IgA Isotype in Human B Cells Encoding Potent Norovirus-Specific Monoclonal Antibodies That Block HBGA Binding</atitle><jtitle>PLoS pathogens</jtitle><addtitle>PLoS Pathog</addtitle><date>2016-06-01</date><risdate>2016</risdate><volume>12</volume><issue>6</issue><spage>e1005719</spage><epage>e1005719</epage><pages>e1005719-e1005719</pages><issn>1553-7374</issn><issn>1553-7366</issn><eissn>1553-7374</eissn><abstract>Noroviruses (NoV) are the most common cause of non-bacterial acute gastroenteritis and cause local outbreaks of illness, especially in confined situations. Despite being identified four decades ago, the correlates of protection against norovirus gastroenteritis are still being elucidated. Recent studies have shown an association of protection with NoV-specific serum histo-blood group antigen-blocking antibody and with serum IgA in patients vaccinated with NoV VLPs. Here, we describe the isolation and characterization of human monoclonal IgG and IgA antibodies against a GI.I NoV, Norwalk virus (NV). A higher proportion of the IgA antibodies blocked NV VLP binding to glycans than did IgG antibodies. We generated isotype-switched variants of IgG and IgA antibodies to study the effects of the constant domain on blocking and binding activities. The IgA form of antibodies appears to be more potent than the IgG form in blocking norovirus binding to histo-blood group antigens. These studies suggest a unique role for IgA antibodies in protection from NoV infections by blocking attachment to cell receptors.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27355511</pmid><doi>10.1371/journal.ppat.1005719</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Antibodies, Monoclonal - immunology Antigens B cells B-Lymphocytes - immunology Biology and Life Sciences Blood Group Antigens - immunology Blood groups Blotting, Western Caliciviridae Infections - immunology Cell Line Chromatography Enzyme-Linked Immunosorbent Assay Epidemics Funding Gastroenteritis Gastroenteritis - immunology Genomes Health aspects Humans Hybridomas Immunoglobulin A Immunoglobulin A - immunology Immunoglobulin G - immunology Immunoglobulins Infections Inventors Medicine and Health Sciences Norovirus Norwalk virus Norwalk virus - immunology Polymerase Chain Reaction Prevention Proteins Research and Analysis Methods Studies Viruses |
| title | Frequent Use of the IgA Isotype in Human B Cells Encoding Potent Norovirus-Specific Monoclonal Antibodies That Block HBGA Binding |
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