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M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain( )
BACKGROUND: Current influenza vaccines are strain specific and demonstrate low vaccine efficacy against H3N2 influenza disease, especially when vaccine is mismatched to circulating virus. The novel influenza vaccine candidate, M2-deficient single replication (M2SR), induces a broad, multi-effector i...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9373152/ https://www.ncbi.nlm.nih.gov/pubmed/34323977 http://dx.doi.org/10.1093/infdis/jiab374 |
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author | Eiden, Joseph Volckaert, Bram Rudenko, Oleg Aitchison, Roger Herber, Renee Belshe, Robert Greenberg, Harry Coelingh, Kathleen Marshall, David Kawaoka, Yoshihiro Neumann, Gabriele Bilsel, Pamuk |
author_facet | Eiden, Joseph Volckaert, Bram Rudenko, Oleg Aitchison, Roger Herber, Renee Belshe, Robert Greenberg, Harry Coelingh, Kathleen Marshall, David Kawaoka, Yoshihiro Neumann, Gabriele Bilsel, Pamuk |
author_sort | Eiden, Joseph |
collection | PubMed |
description | BACKGROUND: Current influenza vaccines are strain specific and demonstrate low vaccine efficacy against H3N2 influenza disease, especially when vaccine is mismatched to circulating virus. The novel influenza vaccine candidate, M2-deficient single replication (M2SR), induces a broad, multi-effector immune response. METHODS: A phase 2 challenge study was conducted to assess the efficacy of an M2SR vaccine expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (Bris2007 M2SR H3N2; clade 1). Four weeks after vaccination, recipients were challenged with antigenically distinct H3N2 virus (A/Belgium/4217/2015, clade 3C.3b) and assessed for infection and clinical symptoms. RESULTS: Adverse events after vaccination were mild and similar in frequency for placebo and M2SR recipients. A single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR recipients were infected after challenge, compared with 71% of placebo recipients. The subset of M2SR recipients with a vaccine-induced microneutralization response against the challenge virus had reduced rates of infection after challenge (38% vs 71% of placebo recipients; P = .050) and reduced illness. CONCLUSIONS: Study participants with vaccine-induced neutralizing antibodies were protected against infection and illness after challenge with an antigenically distinct virus. This is the first demonstration of vaccine-induced protection against a highly drifted H3N2 challenge virus. |
format | Online Article Text |
id | pubmed-9373152 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-93731522022-08-12 M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain( ) Eiden, Joseph Volckaert, Bram Rudenko, Oleg Aitchison, Roger Herber, Renee Belshe, Robert Greenberg, Harry Coelingh, Kathleen Marshall, David Kawaoka, Yoshihiro Neumann, Gabriele Bilsel, Pamuk J Infect Dis Major Article BACKGROUND: Current influenza vaccines are strain specific and demonstrate low vaccine efficacy against H3N2 influenza disease, especially when vaccine is mismatched to circulating virus. The novel influenza vaccine candidate, M2-deficient single replication (M2SR), induces a broad, multi-effector immune response. METHODS: A phase 2 challenge study was conducted to assess the efficacy of an M2SR vaccine expressing hemagglutinin and neuraminidase from A/Brisbane/10/2007 (Bris2007 M2SR H3N2; clade 1). Four weeks after vaccination, recipients were challenged with antigenically distinct H3N2 virus (A/Belgium/4217/2015, clade 3C.3b) and assessed for infection and clinical symptoms. RESULTS: Adverse events after vaccination were mild and similar in frequency for placebo and M2SR recipients. A single dose of Bris2007 M2SR induced neutralizing antibody to the vaccine (48% of recipients) and challenge strain (27% of recipients). Overall, 54% of M2SR recipients were infected after challenge, compared with 71% of placebo recipients. The subset of M2SR recipients with a vaccine-induced microneutralization response against the challenge virus had reduced rates of infection after challenge (38% vs 71% of placebo recipients; P = .050) and reduced illness. CONCLUSIONS: Study participants with vaccine-induced neutralizing antibodies were protected against infection and illness after challenge with an antigenically distinct virus. This is the first demonstration of vaccine-induced protection against a highly drifted H3N2 challenge virus. Oxford University Press 2021-07-29 /pmc/articles/PMC9373152/ /pubmed/34323977 http://dx.doi.org/10.1093/infdis/jiab374 Text en © The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Major Article Eiden, Joseph Volckaert, Bram Rudenko, Oleg Aitchison, Roger Herber, Renee Belshe, Robert Greenberg, Harry Coelingh, Kathleen Marshall, David Kawaoka, Yoshihiro Neumann, Gabriele Bilsel, Pamuk M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain( ) |
title | M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain( ) |
title_full | M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain( ) |
title_fullStr | M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain( ) |
title_full_unstemmed | M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain( ) |
title_short | M2-Deficient Single-Replication Influenza Vaccine–Induced Immune Responses Associated With Protection Against Human Challenge With Highly Drifted H3N2 Influenza Strain( ) |
title_sort | m2-deficient single-replication influenza vaccine–induced immune responses associated with protection against human challenge with highly drifted h3n2 influenza strain( ) |
topic | Major Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9373152/ https://www.ncbi.nlm.nih.gov/pubmed/34323977 http://dx.doi.org/10.1093/infdis/jiab374 |
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