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Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line

Seasonal influenza infections have a significant global impact leading to increased health and economic burden. The efficacy of currently available seasonal influenza vaccines targeting polymorphic surface antigens has historically been suboptimal. Cellular immune responses against highly conserved...

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Autores principales: Folegatti, Pedro M., Bellamy, Duncan, Flaxman, Amy, Mair, Catherine, Ellis, Chris, L. Ramon, Raquel, Ramos Lopez, Fernando, Mitton, Celia, Baker, Megan, Poulton, Ian, Lawrie, Alison, Roberts, Rachel, Minassian, Angela, Ewer, Katie J., Evans, Thomas G., Hill, Adrian V. S., Gilbert, Sarah C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466103/
https://www.ncbi.nlm.nih.gov/pubmed/30909516
http://dx.doi.org/10.3390/vaccines7010033
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author Folegatti, Pedro M.
Bellamy, Duncan
Flaxman, Amy
Mair, Catherine
Ellis, Chris
L. Ramon, Raquel
Ramos Lopez, Fernando
Mitton, Celia
Baker, Megan
Poulton, Ian
Lawrie, Alison
Roberts, Rachel
Minassian, Angela
Ewer, Katie J.
Evans, Thomas G.
Hill, Adrian V. S.
Gilbert, Sarah C.
author_facet Folegatti, Pedro M.
Bellamy, Duncan
Flaxman, Amy
Mair, Catherine
Ellis, Chris
L. Ramon, Raquel
Ramos Lopez, Fernando
Mitton, Celia
Baker, Megan
Poulton, Ian
Lawrie, Alison
Roberts, Rachel
Minassian, Angela
Ewer, Katie J.
Evans, Thomas G.
Hill, Adrian V. S.
Gilbert, Sarah C.
author_sort Folegatti, Pedro M.
collection PubMed
description Seasonal influenza infections have a significant global impact leading to increased health and economic burden. The efficacy of currently available seasonal influenza vaccines targeting polymorphic surface antigens has historically been suboptimal. Cellular immune responses against highly conserved Influenza A virus antigens, such as nucleoprotein (NP) and matrix protein-1 (M1), have previously been shown to be associated with protection from disease, whilst viral-vectored vaccines are an effective strategy to boost cell-mediated immunity. We have previously demonstrated that MVA encoding NP and M1 can induce potent and persistent T cell responses against influenza. In this Phase I study, we evaluated the safety and immunogenicity of MVA-NP+M1, which was newly manufactured on an immortalized cell line, in six healthy adult participants. The vaccine was well-tolerated with only mild to moderate adverse events that resolved spontaneously and were comparable to previous studies with the same vaccine manufactured in chick embryo fibroblasts. A significant increase in vaccine-specific T cell responses was detected seven days after immunization and was directed against both antigens in the vector insert. This small Phase I study supports progression of this vaccine to a Phase IIb study to assess immunogenicity and additional protective efficacy in older adults receiving licensed seasonal influenza vaccines.
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spelling pubmed-64661032019-04-18 Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line Folegatti, Pedro M. Bellamy, Duncan Flaxman, Amy Mair, Catherine Ellis, Chris L. Ramon, Raquel Ramos Lopez, Fernando Mitton, Celia Baker, Megan Poulton, Ian Lawrie, Alison Roberts, Rachel Minassian, Angela Ewer, Katie J. Evans, Thomas G. Hill, Adrian V. S. Gilbert, Sarah C. Vaccines (Basel) Article Seasonal influenza infections have a significant global impact leading to increased health and economic burden. The efficacy of currently available seasonal influenza vaccines targeting polymorphic surface antigens has historically been suboptimal. Cellular immune responses against highly conserved Influenza A virus antigens, such as nucleoprotein (NP) and matrix protein-1 (M1), have previously been shown to be associated with protection from disease, whilst viral-vectored vaccines are an effective strategy to boost cell-mediated immunity. We have previously demonstrated that MVA encoding NP and M1 can induce potent and persistent T cell responses against influenza. In this Phase I study, we evaluated the safety and immunogenicity of MVA-NP+M1, which was newly manufactured on an immortalized cell line, in six healthy adult participants. The vaccine was well-tolerated with only mild to moderate adverse events that resolved spontaneously and were comparable to previous studies with the same vaccine manufactured in chick embryo fibroblasts. A significant increase in vaccine-specific T cell responses was detected seven days after immunization and was directed against both antigens in the vector insert. This small Phase I study supports progression of this vaccine to a Phase IIb study to assess immunogenicity and additional protective efficacy in older adults receiving licensed seasonal influenza vaccines. MDPI 2019-03-22 /pmc/articles/PMC6466103/ /pubmed/30909516 http://dx.doi.org/10.3390/vaccines7010033 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Folegatti, Pedro M.
Bellamy, Duncan
Flaxman, Amy
Mair, Catherine
Ellis, Chris
L. Ramon, Raquel
Ramos Lopez, Fernando
Mitton, Celia
Baker, Megan
Poulton, Ian
Lawrie, Alison
Roberts, Rachel
Minassian, Angela
Ewer, Katie J.
Evans, Thomas G.
Hill, Adrian V. S.
Gilbert, Sarah C.
Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line
title Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line
title_full Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line
title_fullStr Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line
title_full_unstemmed Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line
title_short Safety and Immunogenicity of the Heterosubtypic Influenza A Vaccine MVA-NP+M1 Manufactured on the AGE1.CR.pIX Avian Cell Line
title_sort safety and immunogenicity of the heterosubtypic influenza a vaccine mva-np+m1 manufactured on the age1.cr.pix avian cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466103/
https://www.ncbi.nlm.nih.gov/pubmed/30909516
http://dx.doi.org/10.3390/vaccines7010033
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