Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine

Abstract Live attenuated influenza vaccine (LAIV) is widely used to protect humans from seasonal influenza infection, particularly in children. In contrast to inactivated vaccines, the LAIV can induce both mucosal and cellular immune responses. Here we show that a single dose of monovalent H1N1pdm09...

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Autores principales: Anthony C. Marriott, Karen E. Gooch, Phillip J. Brown, Kathryn A. Ryan, Nicola J. Jones, Natasha Merredew, Nathan Wiblin, Oliver Dibben, Helen Bright, Bassam Hallis, Catherine J. Whittaker, Miles W. Carroll
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/f9f97dcbeef94e3ca43053085c7250dd
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spelling oai:doaj.org-article:f9f97dcbeef94e3ca43053085c7250dd2021-12-02T14:24:55ZSeverity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine10.1038/s41541-021-00306-72059-0105https://doaj.org/article/f9f97dcbeef94e3ca43053085c7250dd2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00306-7https://doaj.org/toc/2059-0105Abstract Live attenuated influenza vaccine (LAIV) is widely used to protect humans from seasonal influenza infection, particularly in children. In contrast to inactivated vaccines, the LAIV can induce both mucosal and cellular immune responses. Here we show that a single dose of monovalent H1N1pdm09-specific LAIV in the ferret model is fully protective against a subsequent wild-type H1N1pdm09 challenge, and furthermore reduces the severity of disease following challenge with a different influenza A subtype (H3N2). The reduced severity comprised reductions in weight loss and fever, as well as more rapid clearance of virus, compared to non-vaccinated H3N2-challenged ferrets. No H3N2-neutralizing antibodies were detected in vaccinated ferret sera. Rather, heterosubtypic protection correlated with interferon-gamma+ (IFN-γ+) T-cell responses measured in peripheral blood and in lung lymphocytes. The IFN-γ+ cells were cross-reactive to H3N2 virus even when obtained from vaccinated animals that had never been exposed to H3N2 virus. We believe this study provides compelling evidence that the LAIV can provide a significant reduction in infection and symptoms when challenged with heterosubtypic influenza strains not included in the LAIV, highlighting the importance of cross-reactive T-cells in the design of a universal influenza vaccine.Anthony C. MarriottKaren E. GoochPhillip J. BrownKathryn A. RyanNicola J. JonesNatasha MerredewNathan WiblinOliver DibbenHelen BrightBassam HallisCatherine J. WhittakerMiles W. CarrollNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-8 (2021)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Immunologic diseases. Allergy
RC581-607
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Anthony C. Marriott
Karen E. Gooch
Phillip J. Brown
Kathryn A. Ryan
Nicola J. Jones
Natasha Merredew
Nathan Wiblin
Oliver Dibben
Helen Bright
Bassam Hallis
Catherine J. Whittaker
Miles W. Carroll
Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine
description Abstract Live attenuated influenza vaccine (LAIV) is widely used to protect humans from seasonal influenza infection, particularly in children. In contrast to inactivated vaccines, the LAIV can induce both mucosal and cellular immune responses. Here we show that a single dose of monovalent H1N1pdm09-specific LAIV in the ferret model is fully protective against a subsequent wild-type H1N1pdm09 challenge, and furthermore reduces the severity of disease following challenge with a different influenza A subtype (H3N2). The reduced severity comprised reductions in weight loss and fever, as well as more rapid clearance of virus, compared to non-vaccinated H3N2-challenged ferrets. No H3N2-neutralizing antibodies were detected in vaccinated ferret sera. Rather, heterosubtypic protection correlated with interferon-gamma+ (IFN-γ+) T-cell responses measured in peripheral blood and in lung lymphocytes. The IFN-γ+ cells were cross-reactive to H3N2 virus even when obtained from vaccinated animals that had never been exposed to H3N2 virus. We believe this study provides compelling evidence that the LAIV can provide a significant reduction in infection and symptoms when challenged with heterosubtypic influenza strains not included in the LAIV, highlighting the importance of cross-reactive T-cells in the design of a universal influenza vaccine.
format article
author Anthony C. Marriott
Karen E. Gooch
Phillip J. Brown
Kathryn A. Ryan
Nicola J. Jones
Natasha Merredew
Nathan Wiblin
Oliver Dibben
Helen Bright
Bassam Hallis
Catherine J. Whittaker
Miles W. Carroll
author_facet Anthony C. Marriott
Karen E. Gooch
Phillip J. Brown
Kathryn A. Ryan
Nicola J. Jones
Natasha Merredew
Nathan Wiblin
Oliver Dibben
Helen Bright
Bassam Hallis
Catherine J. Whittaker
Miles W. Carroll
author_sort Anthony C. Marriott
title Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine
title_short Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine
title_full Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine
title_fullStr Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine
title_full_unstemmed Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine
title_sort severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/f9f97dcbeef94e3ca43053085c7250dd
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