Nasal IgA Provides Protection against Human Influenza Challenge in Volunteers with Low Serum Influenza Antibody Titre
In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of...
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Published in | Frontiers in microbiology Vol. 8; p. 900 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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Frontiers Media S.A
17.05.2017
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Abstract | In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of protection, but other factors may help to reduce viral load or disease severity, for example IgA. In the current study we measured influenza specific responses in a controlled human infection model using influenza A/California/2009 (H1N1) as the challenge agent. Volunteers were pre-selected with low haemagglutination inhibition (HAI) titres in order to ensure a higher proportion of infection; this allowed us to explore the role of other immune correlates. In spite of HAI being uniformly low, there were variable levels of H1N1 specific IgG and IgA prior to infection. There was also a range of disease severity in volunteers allowing us to compare whether differences in systemic and local H1N1 specific IgG and IgA prior to infection affected disease outcome. H1N1 specific IgG level before challenge did not correlate with protection, probably due to the pre-screening for individuals with low HAI. However, the length of time infectious virus was recovered from the nose was reduced in patients with higher pre-existing H1N1 influenza specific nasal IgA or serum IgA. Therefore, IgA contributes to protection against influenza and should be targeted in vaccines. |
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AbstractList | In spite of there being a number of vaccines, influenza remains a significant global cause of morbidity and mortality. Understanding more about natural and vaccine induced immune protection against influenza infection would help to develop better vaccines. Virus specific IgG is a known correlate of protection, but other factors may help to reduce viral load or disease severity, for example IgA. In the current study we measured influenza specific responses in a controlled human infection model using influenza A/California/2009 (H1N1) as the challenge agent. Volunteers were pre-selected with low haemagglutination inhibition (HAI) titres in order to ensure a higher proportion of infection; this allowed us to explore the role of other immune correlates. In spite of HAI being uniformly low, there were variable levels of H1N1 specific IgG and IgA prior to infection. There was also a range of disease severity in volunteers allowing us to compare whether differences in systemic and local H1N1 specific IgG and IgA prior to infection affected disease outcome. H1N1 specific IgG level before challenge did not correlate with protection, probably due to the pre-screening for individuals with low HAI. However, the length of time infectious virus was recovered from the nose was reduced in patients with higher pre-existing H1N1 influenza specific nasal IgA or serum IgA. Therefore, IgA contributes to protection against influenza and should be targeted in vaccines. |
Author | Georges, Bertrand Tregoning, John S Anderson, Katie J Francis, James N Cope, Alethea V Gould, Victoria M W |
AuthorAffiliation | 2 Altimmune, London BioScience Innovation Centre London, United Kingdom 1 Mucosal Infection and Immunity, Section of Virology, Imperial College London London, United Kingdom |
AuthorAffiliation_xml | – name: 1 Mucosal Infection and Immunity, Section of Virology, Imperial College London London, United Kingdom – name: 2 Altimmune, London BioScience Innovation Centre London, United Kingdom |
Author_xml | – sequence: 1 givenname: Victoria M W surname: Gould fullname: Gould, Victoria M W organization: Mucosal Infection and Immunity, Section of Virology, Imperial College LondonLondon, United Kingdom – sequence: 2 givenname: James N surname: Francis fullname: Francis, James N organization: Altimmune, London BioScience Innovation CentreLondon, United Kingdom – sequence: 3 givenname: Katie J surname: Anderson fullname: Anderson, Katie J organization: Altimmune, London BioScience Innovation CentreLondon, United Kingdom – sequence: 4 givenname: Bertrand surname: Georges fullname: Georges, Bertrand organization: Altimmune, London BioScience Innovation CentreLondon, United Kingdom – sequence: 5 givenname: Alethea V surname: Cope fullname: Cope, Alethea V organization: Mucosal Infection and Immunity, Section of Virology, Imperial College LondonLondon, United Kingdom – sequence: 6 givenname: John S surname: Tregoning fullname: Tregoning, John S organization: Mucosal Infection and Immunity, Section of Virology, Imperial College LondonLondon, United Kingdom |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28567036$$D View this record in MEDLINE/PubMed |
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Copyright | Copyright © 2017 Gould, Francis, Anderson, Georges, Cope and Tregoning. 2017 Gould, Francis, Anderson, Georges, Cope and Tregoning |
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Keywords | influenza nasal IgA vaccine Human Infection Challenge study |
Language | English |
License | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Victoria M. W. Gould, MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom Alethea V. Cope, University College London, London, United Kingdom James N. Francis, Autolus Ltd, London, United Kingdom This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology Edited by: Michael W. Cho, Iowa State University, United States Reviewed by: Yasuko Tsunetsugu Yokota, Tokyo University of Technology, Japan; Haider Abdul-Lateef Mousa, University of Basrah, Iraq |
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Title | Nasal IgA Provides Protection against Human Influenza Challenge in Volunteers with Low Serum Influenza Antibody Titre |
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