Optimization of influenza A vaccine virus by reverse genetic using chimeric HA and NA genes with an extended PR8 backbone

Julie Medina; Houda Boukhebza; Amélie De Saint Jean; Régis Sodoyer; Isabelle Legastelois; Catherine Moste

doi:10.1016/j.vaccine.2015.06.112

Optimization of influenza A vaccine virus by reverse genetic using chimeric HA and NA genes with an extended PR8 backbone

Vaccine. 2015 Aug 20;33(35):4221-7. doi: 10.1016/j.vaccine.2015.06.112. Epub 2015 Jul 21.

Authors

Julie Medina¹, Houda Boukhebza², Amélie De Saint Jean³, Régis Sodoyer⁴, Isabelle Legastelois⁵, Catherine Moste⁶

Affiliations

¹ Department of Research and Development, Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy L'Etoile, France. Electronic address: [email protected].
² Department of Research and Development, Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy L'Etoile, France. Electronic address: [email protected].
³ Department of Research and Development, Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy L'Etoile, France. Electronic address: [email protected].
⁴ Department of Research and Development, Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy L'Etoile, France. Electronic address: [email protected].
⁵ Department of Research and Development, Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy L'Etoile, France. Electronic address: [email protected].
⁶ Department of Research and Development, Sanofi Pasteur, 1541 Avenue Marcel Mérieux, 69280 Marcy L'Etoile, France. Electronic address: [email protected].

PMID: 26206270
DOI: 10.1016/j.vaccine.2015.06.112

Abstract

The yield of influenza antigen production may significantly vary between vaccine strains; for example the A/California/07/09 (H1N1)-X179A vaccine virus, prepared during 2009 influenza pandemic, presented a low antigen yield in eggs compared to other seasonal H1N1 reassortants. In this study a bi-chimeric virus expressing HA and NA genes with A/Puerto Rico/8/34 (H1N1) (PR8) and X179A domains was rescued by reverse genetics using a mixture of Vero/CHOK1 cell lines (Medina et al. [7]). The bi-chimeric virus obtained demonstrated to yield much larger amounts of HA than X179A in eggs as measured by single-radial-immunodiffusion (SRID), the reference method to quantify HA protein in influenza vaccine. Such kind of optimized virus using PR8 backbone derived chimeric glycoproteins could be used as improved seed viruses for vaccine production.

Keywords: Chimeric; Influenza; PR8 backbone; Vaccine.

MeSH terms

Amino Acid Sequence
Animals
Antigens, Viral / genetics
Antigens, Viral / immunology
Chlorocebus aethiops
Dogs
Hemagglutinin Glycoproteins, Influenza Virus / chemistry
Hemagglutinin Glycoproteins, Influenza Virus / genetics*
Hemagglutinin Glycoproteins, Influenza Virus / immunology
Humans
Influenza A Virus, H1N1 Subtype / genetics*
Influenza A Virus, H1N1 Subtype / growth & development
Influenza A Virus, H1N1 Subtype / immunology*
Influenza Vaccines / chemistry
Influenza Vaccines / genetics*
Influenza Vaccines / immunology*
Madin Darby Canine Kidney Cells
Molecular Sequence Data
Neuraminidase / genetics*
Reassortant Viruses / genetics
Recombinant Fusion Proteins / chemistry
Recombinant Fusion Proteins / immunology
Reverse Genetics / methods*
Sequence Alignment
Sequence Analysis, DNA
Vero Cells

Substances

Antigens, Viral
Hemagglutinin Glycoproteins, Influenza Virus
Influenza Vaccines
Recombinant Fusion Proteins
Neuraminidase