Cross-Neutralizing Antibodies to Pandemic 2009 H1N1 and Recent Seasonal H1N1 Influenza A Strains Influenced by a Mutation in Hemagglutinin Subunit 2
Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine. We investigated whether sera from persons immunized with the 1976 swine influenza or recent seaso...
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| Published in | PLoS pathogens Vol. 7; no. 6; p. e1002081 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Public Library of Science
01.06.2011
Public Library of Science (PLoS) |
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| Online Access | Get full text |
| ISSN | 1553-7374 1553-7366 1553-7374 |
| DOI | 10.1371/journal.ppat.1002081 |
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| Abstract | Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine. We investigated whether sera from persons immunized with the 1976 swine influenza or recent seasonal influenza vaccines, or both, neutralize 2009 H1N1. Using retroviral pseudovirions bearing hemagglutinins on their surface (HA-pseudotypes), we found that 77% of the sera collected in 1976 after immunization with the A/New Jersey/1976 H1N1 swine influenza vaccine neutralized 2009 H1N1. Forty five percent also neutralized A/New Caledonia/20/1999 H1N1, a strain used in seasonal influenza vaccines during the 2000/01-2006/07 seasons. Among adults aged 48-64 who received the swine influenza vaccine in 1976 and recent seasonal influenza vaccines during the 2004/05-2008/09 seasons, 83% had sera that neutralized 2009 H1N1. However, 68% of age-matched subjects who received the same seasonal influenza vaccines, but did not receive the 1976 swine influenza vaccine, also had sera that neutralized 2009 H1N1. Sera from both 1976 and contemporary cohorts frequently had cross-neutralizing antibodies to 2009 H1N1 and A/New Caledonia/20/1999 that mapped to hemagglutinin subunit 2 (HA2). A conservative mutation in HA2 corresponding to a residue in the A/Solomon Islands/3/2006 and A/Brisbane/59/2007 H1N1 strains that circulated in the 2006/07 and 2007/08 influenza seasons, respectively, abrogated this neutralization. These findings highlight a cross-neutralization determinant influenced by a point mutation in HA2 and suggest that HA2 may be evolving under direct or indirect immune pressure. |
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| AbstractList | Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine. We investigated whether sera from persons immunized with the 1976 swine influenza or recent seasonal influenza vaccines, or both, neutralize 2009 H1N1. Using retroviral pseudovirions bearing hemagglutinins on their surface (HA-pseudotypes), we found that 77% of the sera collected in 1976 after immunization with the A/New Jersey/1976 H1N1 swine influenza vaccine neutralized 2009 H1N1. Forty five percent also neutralized A/New Caledonia/20/1999 H1N1, a strain used in seasonal influenza vaccines during the 2000/01-2006/07 seasons. Among adults aged 48-64 who received the swine influenza vaccine in 1976 and recent seasonal influenza vaccines during the 2004/05-2008/09 seasons, 83% had sera that neutralized 2009 H1N1. However, 68% of age- matched subjects who received the same seasonal influenza vaccines, but did not receive the 1976 swine influenza vaccine, also had sera that neutralized 2009 H1N1. Sera from both 1976 and contemporary cohorts frequently had cross- neutralizing antibodies to 2009 H1N1 and A/New Caledonia/20/1999 that mapped to hemagglutinin subunit 2 (HA2). A conservative mutation in HA2 corresponding to a residue in the A/Solomon Islands/3/2006 and A/Brisbane/59/2007 H1N1 strains that circulated in the 2006/07 and 2007/08 influenza seasons, respectively, abrogated this neutralization. These findings highlight a cross-neutralization determinant influenced by a point mutation in HA2 and suggest that HA2 may be evolving under direct or indirect immune pressure. Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine. We investigated whether sera from persons immunized with the 1976 swine influenza or recent seasonal influenza vaccines, or both, neutralize 2009 H1N1. Using retroviral pseudovirions bearing hemagglutinins on their surface (HA-pseudotypes), we found that 77% of the sera collected in 1976 after immunization with the A/New Jersey/1976 H1N1 swine influenza vaccine neutralized 2009 H1N1. Forty five percent also neutralized A/New Caledonia/20/1999 H1N1, a strain used in seasonal influenza vaccines during the 2000/01-2006/07 seasons. Among adults aged 48-64 who received the swine influenza vaccine in 1976 and recent seasonal influenza vaccines during the 2004/05-2008/09 seasons, 83% had sera that neutralized 2009 H1N1. However, 68% of age-matched subjects who received the same seasonal influenza vaccines, but did not receive the 1976 swine influenza vaccine, also had sera that neutralized 2009 H1N1. Sera from both 1976 and contemporary cohorts frequently had cross-neutralizing antibodies to 2009 H1N1 and A/New Caledonia/20/1999 that mapped to hemagglutinin subunit 2 (HA2). A conservative mutation in HA2 corresponding to a residue in the A/Solomon Islands/3/2006 and A/Brisbane/59/2007 H1N1 strains that circulated in the 2006/07 and 2007/08 influenza seasons, respectively, abrogated this neutralization. These findings highlight a cross-neutralization determinant influenced by a point mutation in HA2 and suggest that HA2 may be evolving under direct or indirect immune pressure. Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine. We investigated whether sera from persons immunized with the 1976 swine influenza or recent seasonal influenza vaccines, or both, neutralize 2009 H1N1. Using retroviral pseudovirions bearing hemagglutinins on their surface (HA-pseudotypes), we found that 77% of the sera collected in 1976 after immunization with the A/New Jersey/1976 H1N1 swine influenza vaccine neutralized 2009 H1N1. Forty five percent also neutralized A/New Caledonia/20/1999 H1N1, a strain used in seasonal influenza vaccines during the 2000/01-2006/07 seasons. Among adults aged 48-64 who received the swine influenza vaccine in 1976 and recent seasonal influenza vaccines during the 2004/05-2008/09 seasons, 83% had sera that neutralized 2009 H1N1. However, 68% of age-matched subjects who received the same seasonal influenza vaccines, but did not receive the 1976 swine influenza vaccine, also had sera that neutralized 2009 H1N1. Sera from both 1976 and contemporary cohorts frequently had cross-neutralizing antibodies to 2009 H1N1 and A/New Caledonia/20/1999 that mapped to hemagglutinin subunit 2 (HA2). A conservative mutation in HA2 corresponding to a residue in the A/Solomon Islands/3/2006 and A/Brisbane/59/2007 H1N1 strains that circulated in the 2006/07 and 2007/08 influenza seasons, respectively, abrogated this neutralization. These findings highlight a cross-neutralization determinant influenced by a point mutation in HA2 and suggest that HA2 may be evolving under direct or indirect immune pressure.Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine. We investigated whether sera from persons immunized with the 1976 swine influenza or recent seasonal influenza vaccines, or both, neutralize 2009 H1N1. Using retroviral pseudovirions bearing hemagglutinins on their surface (HA-pseudotypes), we found that 77% of the sera collected in 1976 after immunization with the A/New Jersey/1976 H1N1 swine influenza vaccine neutralized 2009 H1N1. Forty five percent also neutralized A/New Caledonia/20/1999 H1N1, a strain used in seasonal influenza vaccines during the 2000/01-2006/07 seasons. Among adults aged 48-64 who received the swine influenza vaccine in 1976 and recent seasonal influenza vaccines during the 2004/05-2008/09 seasons, 83% had sera that neutralized 2009 H1N1. However, 68% of age-matched subjects who received the same seasonal influenza vaccines, but did not receive the 1976 swine influenza vaccine, also had sera that neutralized 2009 H1N1. Sera from both 1976 and contemporary cohorts frequently had cross-neutralizing antibodies to 2009 H1N1 and A/New Caledonia/20/1999 that mapped to hemagglutinin subunit 2 (HA2). A conservative mutation in HA2 corresponding to a residue in the A/Solomon Islands/3/2006 and A/Brisbane/59/2007 H1N1 strains that circulated in the 2006/07 and 2007/08 influenza seasons, respectively, abrogated this neutralization. These findings highlight a cross-neutralization determinant influenced by a point mutation in HA2 and suggest that HA2 may be evolving under direct or indirect immune pressure. Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine. We investigated whether sera from persons immunized with the 1976 swine influenza or recent seasonal influenza vaccines, or both, neutralize 2009 H1N1. Using retroviral pseudovirions bearing hemagglutinins on their surface (HA-pseudotypes), we found that 77% of the sera collected in 1976 after immunization with the A/New Jersey/1976 H1N1 swine influenza vaccine neutralized 2009 H1N1. Forty five percent also neutralized A/New Caledonia/20/1999 H1N1, a strain used in seasonal influenza vaccines during the 2000/01–2006/07 seasons. Among adults aged 48–64 who received the swine influenza vaccine in 1976 and recent seasonal influenza vaccines during the 2004/05–2008/09 seasons, 83% had sera that neutralized 2009 H1N1. However, 68% of age-matched subjects who received the same seasonal influenza vaccines, but did not receive the 1976 swine influenza vaccine, also had sera that neutralized 2009 H1N1. Sera from both 1976 and contemporary cohorts frequently had cross-neutralizing antibodies to 2009 H1N1 and A/New Caledonia/20/1999 that mapped to hemagglutinin subunit 2 (HA2). A conservative mutation in HA2 corresponding to a residue in the A/Solomon Islands/3/2006 and A/Brisbane/59/2007 H1N1 strains that circulated in the 2006/07 and 2007/08 influenza seasons, respectively, abrogated this neutralization. These findings highlight a cross-neutralization determinant influenced by a point mutation in HA2 and suggest that HA2 may be evolving under direct or indirect immune pressure. Influenza A viruses mutate to escape neutralization by antibodies. These mutations predominantly occur in the globular head of the hemagglutinin protein, while the stalk is more conserved. Pandemic 2009 H1N1 influenza virus differs from seasonal H1N1 strains that circulated in the past 50 years and resembles a strain that did not circulate but was used in the 1976 swine influenza vaccine. We investigated whether persons immunized with either the 1976 swine influenza or recent seasonal influenza vaccines, or both, have antibodies that cross-neutralize pandemic 2009 H1N1. Sera from 1976 swine influenza vaccine trials cross-neutralized pandemic 2009 H1N1 and to a lesser extent the A/New Caledonia/20/1999 H1N1 strain that was used in vaccines during the 2000/01–2006/07 influenza seasons. Sera from persons who received several seasonal influenza vaccines containing A/New Caledonia/20/1999 H1N1 cross-neutralized pandemic 2009 H1N1, regardless of whether they received the 1976 swine influenza vaccine. We found that cross-neutralization between 2009 H1N1 and A/New Caledonia/20/1999 frequently mapped to the hemagglutinin stalk. A mutation in the stalk of strains circulating during the 2007/08–2008/09 seasons abrogates this neutralization. These findings highlight a cross-neutralization determinant influenced by a point mutation in the hemagglutinin stalk and suggest that the stalk may be evolving under direct or indirect immune pressure. |
| Audience | Academic |
| Author | Yang, Hong Vassell, Russell Wang, Wei Ye, Zhiping Anderson, Christine M. Zhuang, Min Xie, Hang Scott, Dorothy De Feo, Christopher J. Weiss, Carol D. |
| AuthorAffiliation | 2 Division of Hematology, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland, United States of America 4 Laboratory of Pediatric and Respiratory Diseases, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland, United States of America 1 Laboratory of Immunoregulation, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland, United States of America 3 Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland, United States of America Johns Hopkins University - Bloomberg School of Public Health, United States of America |
| AuthorAffiliation_xml | – name: 2 Division of Hematology, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland, United States of America – name: 4 Laboratory of Pediatric and Respiratory Diseases, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland, United States of America – name: 1 Laboratory of Immunoregulation, Division of Viral Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland, United States of America – name: 3 Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, US Food and Drug Administration, Bethesda, Maryland, United States of America – name: Johns Hopkins University - Bloomberg School of Public Health, United States of America |
| Author_xml | – sequence: 1 givenname: Wei surname: Wang fullname: Wang, Wei – sequence: 2 givenname: Christine M. surname: Anderson fullname: Anderson, Christine M. – sequence: 3 givenname: Christopher J. surname: De Feo fullname: De Feo, Christopher J. – sequence: 4 givenname: Min surname: Zhuang fullname: Zhuang, Min – sequence: 5 givenname: Hong surname: Yang fullname: Yang, Hong – sequence: 6 givenname: Russell surname: Vassell fullname: Vassell, Russell – sequence: 7 givenname: Hang surname: Xie fullname: Xie, Hang – sequence: 8 givenname: Zhiping surname: Ye fullname: Ye, Zhiping – sequence: 9 givenname: Dorothy surname: Scott fullname: Scott, Dorothy – sequence: 10 givenname: Carol D. surname: Weiss fullname: Weiss, Carol D. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21695241$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2011 Public Library of Science 2011 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: Citation: Wang W, Anderson CM, De Feo CJ, Zhuang M, Yang H, et al. (2011) Cross-Neutralizing Antibodies to Pandemic 2009 H1N1 and Recent Seasonal H1N1 Influenza A Strains Influenced by a Mutation in Hemagglutinin Subunit 2. PLoS Pathog 7(6): e1002081. doi:10.1371/journal.ppat.1002081 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. 2011 2011 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: Citation: Wang W, Anderson CM, De Feo CJ, Zhuang M, Yang H, et al. (2011) Cross-Neutralizing Antibodies to Pandemic 2009 H1N1 and Recent Seasonal H1N1 Influenza A Strains Influenced by a Mutation in Hemagglutinin Subunit 2. PLoS Pathog 7(6): e1002081. doi:10.1371/journal.ppat.1002081 |
| Copyright_xml | – notice: COPYRIGHT 2011 Public Library of Science – notice: 2011 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: Citation: Wang W, Anderson CM, De Feo CJ, Zhuang M, Yang H, et al. (2011) Cross-Neutralizing Antibodies to Pandemic 2009 H1N1 and Recent Seasonal H1N1 Influenza A Strains Influenced by a Mutation in Hemagglutinin Subunit 2. PLoS Pathog 7(6): e1002081. doi:10.1371/journal.ppat.1002081 – notice: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. 2011 – notice: 2011 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: Citation: Wang W, Anderson CM, De Feo CJ, Zhuang M, Yang H, et al. (2011) Cross-Neutralizing Antibodies to Pandemic 2009 H1N1 and Recent Seasonal H1N1 Influenza A Strains Influenced by a Mutation in Hemagglutinin Subunit 2. PLoS Pathog 7(6): e1002081. doi:10.1371/journal.ppat.1002081 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Conceived and designed the experiments: WW CDW. Performed the experiments: WW MZ. Analyzed the data: WW CJD HY CDW. Contributed reagents/materials/analysis tools: WW CMA DS RV HX ZY CDW. Wrote the paper: WW CJD CDW. |
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| Snippet | Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1... Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1... |
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| SubjectTerms | Antibodies, Neutralizing Biology Cell Line Cross Reactions - immunology Gene mutations Genetic aspects Health aspects Hemagglutinins - genetics Humans Immunization Influenza A Virus, H1N1 Subtype - classification Influenza A Virus, H1N1 Subtype - immunology Influenza vaccines Influenza Vaccines - immunology Medicine Mutation Neutralization Pandemics Point Mutation Protein Subunits - genetics Seasons Swine flu Swine influenza Vaccination Vaccines Viruses |
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| Title | Cross-Neutralizing Antibodies to Pandemic 2009 H1N1 and Recent Seasonal H1N1 Influenza A Strains Influenced by a Mutation in Hemagglutinin Subunit 2 |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/21695241 https://www.proquest.com/docview/1289069771 https://www.proquest.com/docview/873495401 https://pubmed.ncbi.nlm.nih.gov/PMC3111540 https://doaj.org/article/4b7e204274c641c690440b508b464741 http://dx.doi.org/10.1371/journal.ppat.1002081 |
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