tetano
Editor, Senior Moderator
Vaccine
Volume 31, Issue 1, 17 December 2012, Pages 207?212
Cover image
Mutations to A/Puerto Rico/8/34 PB1 gene improves seasonal reassortant influenza A virus growth kinetics
Ewan P. Plant,
Teresa M. Liu,
Hang Xie,
Zhiping YeCorresponding author contact information, E-mail the corresponding author
Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, MD 20892, United States
http://dx.doi.org/10.1016/j.vaccine.2012.10.060
It is desirable for influenza vaccine virus strains to have phenotypes that include good growth and hemagglutinin (HA) protein yield. The quality of these characteristics varies among the vaccine viruses and is usually due to multigenic effects. Many influenza A virus vaccine viruses are made as reassortants of the high yield virus A/Puerto Rico/8/34 (PR/8) and a circulating seasonal virus. Co-infection of eggs with the two viruses, and selection of reassortants with the HA and neuraminidase (NA) segments from the seasonal virus, can result in viruses that contain a mixture of internal genes derived from both the high yield virus and the circulating virus. Segment 2 (PB1), which encodes the RNA-dependent RNA polymerase, frequently cosegregates with the seasonal HA and NA segments. We asked whether mutations based on the seasonal PB1 genes could improve vaccine virus strains. Here we report that mutations to the PR/8 PB1 gene, based on differences observed between seasonal and PR/8 PB1 genes, accelerate egg and cell culture based replication for a reassortant virus containing HA and NA segments from the low yield A/Wyoming/03/2003 (H3N2) vaccine virus.
Highlights
► Influenza vaccine strains contain variant PB1 genes. ► Targeted mutagenesis of PR/8 PB1 can improve vaccine strain characteristics. ► Specific PB1 mutations enhance growth of poorly growing virus. ► Specific PB1 mutations increase protein yield in allantoic fluid at early time points.
http://www.sciencedirect.com/science/article/pii/S0264410X12015083
Volume 31, Issue 1, 17 December 2012, Pages 207?212
Cover image
Mutations to A/Puerto Rico/8/34 PB1 gene improves seasonal reassortant influenza A virus growth kinetics
Ewan P. Plant,
Teresa M. Liu,
Hang Xie,
Zhiping YeCorresponding author contact information, E-mail the corresponding author
Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, MD 20892, United States
http://dx.doi.org/10.1016/j.vaccine.2012.10.060
It is desirable for influenza vaccine virus strains to have phenotypes that include good growth and hemagglutinin (HA) protein yield. The quality of these characteristics varies among the vaccine viruses and is usually due to multigenic effects. Many influenza A virus vaccine viruses are made as reassortants of the high yield virus A/Puerto Rico/8/34 (PR/8) and a circulating seasonal virus. Co-infection of eggs with the two viruses, and selection of reassortants with the HA and neuraminidase (NA) segments from the seasonal virus, can result in viruses that contain a mixture of internal genes derived from both the high yield virus and the circulating virus. Segment 2 (PB1), which encodes the RNA-dependent RNA polymerase, frequently cosegregates with the seasonal HA and NA segments. We asked whether mutations based on the seasonal PB1 genes could improve vaccine virus strains. Here we report that mutations to the PR/8 PB1 gene, based on differences observed between seasonal and PR/8 PB1 genes, accelerate egg and cell culture based replication for a reassortant virus containing HA and NA segments from the low yield A/Wyoming/03/2003 (H3N2) vaccine virus.
Highlights
► Influenza vaccine strains contain variant PB1 genes. ► Targeted mutagenesis of PR/8 PB1 can improve vaccine strain characteristics. ► Specific PB1 mutations enhance growth of poorly growing virus. ► Specific PB1 mutations increase protein yield in allantoic fluid at early time points.
http://www.sciencedirect.com/science/article/pii/S0264410X12015083