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Identification of the properties of H5 influenza vaccine viruses with high hemagglutinin yields
Manufactured influenza vaccines have to contain a defined amount of hemagglutinin (HA) antigen. Therefore, vaccine viruses with a high HA antigen yield (HAY) are preferable for manufacturing vaccines, particularly vaccines in response to a pandemic, when vaccines need to be rapidly produced. However...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9858889/ https://www.ncbi.nlm.nih.gov/pubmed/36662890 http://dx.doi.org/10.1371/journal.pone.0280811 |
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author | Arita, Tomoko Suzuki, Yasushi Shimasaki, Noriko Kobayashi, Hirotaka Hasegawa, Hideki Odagiri, Takato Tashiro, Masato Nobusawa, Eri |
author_facet | Arita, Tomoko Suzuki, Yasushi Shimasaki, Noriko Kobayashi, Hirotaka Hasegawa, Hideki Odagiri, Takato Tashiro, Masato Nobusawa, Eri |
author_sort | Arita, Tomoko |
collection | PubMed |
description | Manufactured influenza vaccines have to contain a defined amount of hemagglutinin (HA) antigen. Therefore, vaccine viruses with a high HA antigen yield (HAY) are preferable for manufacturing vaccines, particularly vaccines in response to a pandemic, when vaccines need to be rapidly produced. However, the viral properties associated with a high HAY have not yet been fully clarified. To identify the HAY-associated traits, we first propagated 26 H5 candidate vaccine viruses (CVVs) in eggs, which were previously developed based on genetic reassortment methods using master viruses, to determine their total protein yield (TPY), ratio of HA to total viral protein (%-HA content) and HAY. The results revealed that the HAY was correlated with the TPY but not with the %-HA content. We further found that altering the sequences of the 3’ noncoding region of HA vRNA or replacing the master virus improved the HAYs and TPYs of the low-HAY CVVs to approximately double the values of the original CVVs but did not change the %-HA content, which a previous study suggested was associated with the HAY. Analyses based on real-time PCR assays and scanning electron microscopy revealed that the virus samples with an improved HAY contained more copies of the virus genome and viral particles than the original samples. The results suggest that an improvement in virus growth (i.e., an increase in the amount of viral particles) leads to an increase in the TPY and thus in the HAY, regardless of the %-HA content. The approximately twofold increase in the HAY shown in this study may not appear to represent a large improvement, but the impact will be significant given the millions of chicken eggs used to produce vaccines. These findings will be informative for developing high-HAY vaccine viruses. |
format | Online Article Text |
id | pubmed-9858889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-98588892023-01-21 Identification of the properties of H5 influenza vaccine viruses with high hemagglutinin yields Arita, Tomoko Suzuki, Yasushi Shimasaki, Noriko Kobayashi, Hirotaka Hasegawa, Hideki Odagiri, Takato Tashiro, Masato Nobusawa, Eri PLoS One Research Article Manufactured influenza vaccines have to contain a defined amount of hemagglutinin (HA) antigen. Therefore, vaccine viruses with a high HA antigen yield (HAY) are preferable for manufacturing vaccines, particularly vaccines in response to a pandemic, when vaccines need to be rapidly produced. However, the viral properties associated with a high HAY have not yet been fully clarified. To identify the HAY-associated traits, we first propagated 26 H5 candidate vaccine viruses (CVVs) in eggs, which were previously developed based on genetic reassortment methods using master viruses, to determine their total protein yield (TPY), ratio of HA to total viral protein (%-HA content) and HAY. The results revealed that the HAY was correlated with the TPY but not with the %-HA content. We further found that altering the sequences of the 3’ noncoding region of HA vRNA or replacing the master virus improved the HAYs and TPYs of the low-HAY CVVs to approximately double the values of the original CVVs but did not change the %-HA content, which a previous study suggested was associated with the HAY. Analyses based on real-time PCR assays and scanning electron microscopy revealed that the virus samples with an improved HAY contained more copies of the virus genome and viral particles than the original samples. The results suggest that an improvement in virus growth (i.e., an increase in the amount of viral particles) leads to an increase in the TPY and thus in the HAY, regardless of the %-HA content. The approximately twofold increase in the HAY shown in this study may not appear to represent a large improvement, but the impact will be significant given the millions of chicken eggs used to produce vaccines. These findings will be informative for developing high-HAY vaccine viruses. Public Library of Science 2023-01-20 /pmc/articles/PMC9858889/ /pubmed/36662890 http://dx.doi.org/10.1371/journal.pone.0280811 Text en © 2023 Arita et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Arita, Tomoko Suzuki, Yasushi Shimasaki, Noriko Kobayashi, Hirotaka Hasegawa, Hideki Odagiri, Takato Tashiro, Masato Nobusawa, Eri Identification of the properties of H5 influenza vaccine viruses with high hemagglutinin yields |
title | Identification of the properties of H5 influenza vaccine viruses with high hemagglutinin yields |
title_full | Identification of the properties of H5 influenza vaccine viruses with high hemagglutinin yields |
title_fullStr | Identification of the properties of H5 influenza vaccine viruses with high hemagglutinin yields |
title_full_unstemmed | Identification of the properties of H5 influenza vaccine viruses with high hemagglutinin yields |
title_short | Identification of the properties of H5 influenza vaccine viruses with high hemagglutinin yields |
title_sort | identification of the properties of h5 influenza vaccine viruses with high hemagglutinin yields |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9858889/ https://www.ncbi.nlm.nih.gov/pubmed/36662890 http://dx.doi.org/10.1371/journal.pone.0280811 |
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