Rapid generation of a well-matched vaccine seed from a modern influenza A virus primary isolate without recourse to eggs

L. C.S. Hartgroves; W. Koudstaal; C. McLeod; O. Moncorgé; C. I. Thompson; J. Ellis; C. Bull; M. J.E. Havenga; J. Goudsmit; W. S. Barclay

doi:10.1016/j.vaccine.2010.02.012

Rapid generation of a well-matched vaccine seed from a modern influenza A virus primary isolate without recourse to eggs

L. C.S. Hartgroves, W. Koudstaal, C. McLeod, O. Moncorgé, C. I. Thompson, J. Ellis, C. Bull, M. J.E. Havenga, J. Goudsmit, W. S. Barclay^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Most influenza vaccines are produced in chicken eggs but recent human influenza strains often do not grow well in this substrate. The PER.C6^® cell line is an alternative platform for vaccine production. Here we demonstrate that PER.C6 cells faithfully propagate recent clinical isolates, without selecting for mutations in the HA gene. PER.C6 cells support the rescue of recombinant influenza viruses from cDNA. We used sequence data from a surveillance programme to generate a PR8-based seed virus with the HA and NA of a contemporary circulating H3N2 human strain, A/England/611/07 (E611) that did not itself grow in eggs. We engineered mutations that affected receptor-binding, G186V or L194P, into the E611 HA gene. Whilst the L194P mutation conferred efficient growth in eggs, G186V did not. The L194P mutation was also spontaneously selected during egg propagation of E611/PR8 7:1 recombinant virus. This suggests generation of a single recombinant vaccine seed might satisfy manufacturers that utilize either eggs or cells for vaccine production.

Original language	English
Pages (from-to)	2973-2979
Number of pages	7
Journal	Vaccine
Volume	28
Issue number	17
DOIs	https://doi.org/10.1016/j.vaccine.2010.02.012
Publication status	Published - 9 Apr 2010

Bibliographical note

Funding Information:
PER.C6 ® is a registered trademark owned by Crucell Holland B.V. This work was funded by Sanofi-Pasteur and Crucell Holland B.V.

Keywords

Influenza
Reverse genetics
Vaccine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.vaccine.2010.02.012

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title = "Rapid generation of a well-matched vaccine seed from a modern influenza A virus primary isolate without recourse to eggs",

abstract = "Most influenza vaccines are produced in chicken eggs but recent human influenza strains often do not grow well in this substrate. The PER.C6{\textregistered} cell line is an alternative platform for vaccine production. Here we demonstrate that PER.C6 cells faithfully propagate recent clinical isolates, without selecting for mutations in the HA gene. PER.C6 cells support the rescue of recombinant influenza viruses from cDNA. We used sequence data from a surveillance programme to generate a PR8-based seed virus with the HA and NA of a contemporary circulating H3N2 human strain, A/England/611/07 (E611) that did not itself grow in eggs. We engineered mutations that affected receptor-binding, G186V or L194P, into the E611 HA gene. Whilst the L194P mutation conferred efficient growth in eggs, G186V did not. The L194P mutation was also spontaneously selected during egg propagation of E611/PR8 7:1 recombinant virus. This suggests generation of a single recombinant vaccine seed might satisfy manufacturers that utilize either eggs or cells for vaccine production.",

keywords = "Influenza, Reverse genetics, Vaccine",

author = "Hartgroves, {L. C.S.} and W. Koudstaal and C. McLeod and O. Moncorg{\'e} and Thompson, {C. I.} and J. Ellis and C. Bull and Havenga, {M. J.E.} and J. Goudsmit and Barclay, {W. S.}",

note = "Funding Information: PER.C6 {\textregistered} is a registered trademark owned by Crucell Holland B.V. This work was funded by Sanofi-Pasteur and Crucell Holland B.V.",

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AU - Hartgroves, L. C.S.

AU - Koudstaal, W.

AU - McLeod, C.

AU - Moncorgé, O.

AU - Thompson, C. I.

AU - Ellis, J.

AU - Bull, C.

AU - Havenga, M. J.E.

AU - Goudsmit, J.

AU - Barclay, W. S.

N1 - Funding Information: PER.C6 ® is a registered trademark owned by Crucell Holland B.V. This work was funded by Sanofi-Pasteur and Crucell Holland B.V.

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N2 - Most influenza vaccines are produced in chicken eggs but recent human influenza strains often do not grow well in this substrate. The PER.C6® cell line is an alternative platform for vaccine production. Here we demonstrate that PER.C6 cells faithfully propagate recent clinical isolates, without selecting for mutations in the HA gene. PER.C6 cells support the rescue of recombinant influenza viruses from cDNA. We used sequence data from a surveillance programme to generate a PR8-based seed virus with the HA and NA of a contemporary circulating H3N2 human strain, A/England/611/07 (E611) that did not itself grow in eggs. We engineered mutations that affected receptor-binding, G186V or L194P, into the E611 HA gene. Whilst the L194P mutation conferred efficient growth in eggs, G186V did not. The L194P mutation was also spontaneously selected during egg propagation of E611/PR8 7:1 recombinant virus. This suggests generation of a single recombinant vaccine seed might satisfy manufacturers that utilize either eggs or cells for vaccine production.

AB - Most influenza vaccines are produced in chicken eggs but recent human influenza strains often do not grow well in this substrate. The PER.C6® cell line is an alternative platform for vaccine production. Here we demonstrate that PER.C6 cells faithfully propagate recent clinical isolates, without selecting for mutations in the HA gene. PER.C6 cells support the rescue of recombinant influenza viruses from cDNA. We used sequence data from a surveillance programme to generate a PR8-based seed virus with the HA and NA of a contemporary circulating H3N2 human strain, A/England/611/07 (E611) that did not itself grow in eggs. We engineered mutations that affected receptor-binding, G186V or L194P, into the E611 HA gene. Whilst the L194P mutation conferred efficient growth in eggs, G186V did not. The L194P mutation was also spontaneously selected during egg propagation of E611/PR8 7:1 recombinant virus. This suggests generation of a single recombinant vaccine seed might satisfy manufacturers that utilize either eggs or cells for vaccine production.

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KW - Reverse genetics

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Rapid generation of a well-matched vaccine seed from a modern influenza A virus primary isolate without recourse to eggs

Abstract

Bibliographical note

Keywords

UN SDGs

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