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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...

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Autores principales: Arita, Tomoko, Suzuki, Yasushi, Shimasaki, Noriko, Kobayashi, Hirotaka, Hasegawa, Hideki, Odagiri, Takato, Tashiro, Masato, Nobusawa, Eri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
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.
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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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