tetano
Editor, Senior Moderator
J Virol. 2013 Mar 6. [Epub ahead of print]
The source of the PB1 gene in influenza vaccine reassortants selectively alters HA content of the resulting seed virus.
Cobbin JC, Verity EE, Gilbertson BP, Rockman SP, Brown LE.
Source
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Abstract
Yields of egg-grown influenza vaccines are maximised by production of a seed strain using reassortment of the seasonal influenza isolate with a highly egg-adapted strain. The seed virus is selected based on high yields of viral hemagglutinin (HA) and expression of the surface antigens from the seasonal isolate. The remaining proteins are usually derived from the high-growth parent. However a retrospective analysis of vaccine seeds revealed that the seasonal PB1 gene was selected in greater than 50% of reassortment events. Using the model seasonal H3N2 virus A/Udorn/307/72 (Udorn) and the high-growth A/Puerto Rico/8/34 (PR8) virus we assessed the influence of the source of the PB1 gene on virus growth and vaccine yield. Classical reassortment of these two strains led to the selection of viruses that predominantly had the Udorn PB1 gene. The presence of Udorn PB1 in the seed virus, however, did not result in higher yields of virus or HA compared to the corresponding seed virus with PR8 PB1. The 8-fold fewer virions produced with the seed virus containing the Udorn PB1 was somewhat compensated for by a 4-fold increase in HA per virion. A higher HA/nucleoprotein (NP) ratio was found in past vaccine preparations when the seasonal PB1 was present, also indicative of a higher HA density in these vaccine viruses. As HA vRNA and mRNA levels in infected cells were similar we propose that PB1 selectively alters the translation of viral mRNA. This study helps to explain the variability of vaccine seeds with respect to HA yield.
PMID:
23468502
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23468502
The source of the PB1 gene in influenza vaccine reassortants selectively alters HA content of the resulting seed virus.
Cobbin JC, Verity EE, Gilbertson BP, Rockman SP, Brown LE.
Source
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Abstract
Yields of egg-grown influenza vaccines are maximised by production of a seed strain using reassortment of the seasonal influenza isolate with a highly egg-adapted strain. The seed virus is selected based on high yields of viral hemagglutinin (HA) and expression of the surface antigens from the seasonal isolate. The remaining proteins are usually derived from the high-growth parent. However a retrospective analysis of vaccine seeds revealed that the seasonal PB1 gene was selected in greater than 50% of reassortment events. Using the model seasonal H3N2 virus A/Udorn/307/72 (Udorn) and the high-growth A/Puerto Rico/8/34 (PR8) virus we assessed the influence of the source of the PB1 gene on virus growth and vaccine yield. Classical reassortment of these two strains led to the selection of viruses that predominantly had the Udorn PB1 gene. The presence of Udorn PB1 in the seed virus, however, did not result in higher yields of virus or HA compared to the corresponding seed virus with PR8 PB1. The 8-fold fewer virions produced with the seed virus containing the Udorn PB1 was somewhat compensated for by a 4-fold increase in HA per virion. A higher HA/nucleoprotein (NP) ratio was found in past vaccine preparations when the seasonal PB1 was present, also indicative of a higher HA density in these vaccine viruses. As HA vRNA and mRNA levels in infected cells were similar we propose that PB1 selectively alters the translation of viral mRNA. This study helps to explain the variability of vaccine seeds with respect to HA yield.
PMID:
23468502
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23468502