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Vaccine
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doi:10.1016/j.vaccine.2011.11.081 | How to Cite or Link Using DOI
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An additional oligosaccharide moiety in the HA of a pandemic influenza H1N1 candidate vaccine virus confers increased antigen yield in eggs
Carolyn Nicolson Corresponding Author Contact Information, E-mail The Corresponding Author, Ruth Harvey, E-mail The Corresponding Author, Rachel Johnson, E-mail The Corresponding Author, Kate Guilfoyle, E-mail The Corresponding Author, Othmar G. Engelhardt, E-mail The Corresponding Author, James S. Robertson, E-mail The Corresponding Author
Division of Virology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK
Received 18 August 2011; revised 17 November 2011; Accepted 18 November 2011. Available online 30 November 2011.
Abstract
The H1N1 influenza pandemic in 2009 highlighted the need for the rapid generation of candidate vaccine viruses (CVVs) against an A/California/7/2009-like virus. The first available CVVs gave low protein yields in eggs but improved yields were achieved for second generation CVVs which contained amino acid substitutions compared to their precursor viruses. In this study, we investigated the basis for the increased virus protein yield of CVV NIBRG-121xp and whether the improved yield characteristics could be transferred between this virus and two other CVVs, NYMC X-179A and NYMC X-181. We generated variant viruses by reverse genetics to contain combinations of amino acid substitutions found in high yielding NIBRG-121xp and NYMC X-181. We found that the increase in total protein yield and functional HA yield of NIBRG-121xp in eggs is attributable to the single amino acid substitution K119N in the HA. We also found that the glycosylation of position 119 is essential for the improved virus protein yield in eggs. However, the K119N yield-enhancing effect was not transferable between viruses, nor was the N129D change found in high yielding NYMC X-181. However, position 119 may be a useful locus to monitor in future for viruses and CVVs with potentially high yield.
Highlights
► HA substitutions in influenza pandemic H1N1 vaccine were analysed. ► Specific substitutions affecting increased antigen yield identified. ► A specific novel glycosylation site is associated with increased yield. ► Substitutions affecting yield were not transferrable between vaccine viruses.
http://www.sciencedirect.com/science/article/pii/S0264410X11018779
In Press, Uncorrected Proof - Note to users
doi:10.1016/j.vaccine.2011.11.081 | How to Cite or Link Using DOI
Permissions & Reprints
An additional oligosaccharide moiety in the HA of a pandemic influenza H1N1 candidate vaccine virus confers increased antigen yield in eggs
Carolyn Nicolson Corresponding Author Contact Information, E-mail The Corresponding Author, Ruth Harvey, E-mail The Corresponding Author, Rachel Johnson, E-mail The Corresponding Author, Kate Guilfoyle, E-mail The Corresponding Author, Othmar G. Engelhardt, E-mail The Corresponding Author, James S. Robertson, E-mail The Corresponding Author
Division of Virology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK
Received 18 August 2011; revised 17 November 2011; Accepted 18 November 2011. Available online 30 November 2011.
Abstract
The H1N1 influenza pandemic in 2009 highlighted the need for the rapid generation of candidate vaccine viruses (CVVs) against an A/California/7/2009-like virus. The first available CVVs gave low protein yields in eggs but improved yields were achieved for second generation CVVs which contained amino acid substitutions compared to their precursor viruses. In this study, we investigated the basis for the increased virus protein yield of CVV NIBRG-121xp and whether the improved yield characteristics could be transferred between this virus and two other CVVs, NYMC X-179A and NYMC X-181. We generated variant viruses by reverse genetics to contain combinations of amino acid substitutions found in high yielding NIBRG-121xp and NYMC X-181. We found that the increase in total protein yield and functional HA yield of NIBRG-121xp in eggs is attributable to the single amino acid substitution K119N in the HA. We also found that the glycosylation of position 119 is essential for the improved virus protein yield in eggs. However, the K119N yield-enhancing effect was not transferable between viruses, nor was the N129D change found in high yielding NYMC X-181. However, position 119 may be a useful locus to monitor in future for viruses and CVVs with potentially high yield.
Highlights
► HA substitutions in influenza pandemic H1N1 vaccine were analysed. ► Specific substitutions affecting increased antigen yield identified. ► A specific novel glycosylation site is associated with increased yield. ► Substitutions affecting yield were not transferrable between vaccine viruses.
http://www.sciencedirect.com/science/article/pii/S0264410X11018779