Cold adaptation generates mutations associated with the growth of influenza B vaccine viruses. Issue 43 (26th October 2015)

• Record Type: Journal Article
• Authors: Kim, Hyunsuh; Velkov, Tony; Camuglia, Sarina; Rockman, Steven P.; Tannock, Gregory A.
• Is Part Of: Vaccine. Volume 33:Issue 43(2015)
• Page Start: 5786
• Page End: 5793
• Publication Date: 2015-10-26
• Subjects: Influenza B virus -- Vaccine -- Growth -- Mutations -- Cold adaptation; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.09.038
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: HA yields of influenza B viruses used in vaccine manufacture are often unpredictable and inadequate. Preparation of high-yielding influenza B vaccine seed viruses by reassortment has proven difficult. Mutations associated with the growth of influenza B vaccine viruses have been identified. This study has the potential to allow improved predictability in the manufacture of influenza vaccines. Abstract: Seasonal inactivated influenza vaccines are usually trivalent or quadrivalent and are prepared from accredited seed viruses. Yields of influenza A seed viruses can be enhanced by gene reassortment with high-yielding donor strains, but similar approaches for influenza B seed viruses have been largely unsuccessful. For vaccine manufacture influenza B seed viruses are usually adapted for high- growth by serial passage. Influenza B antigen yields so obtained are often unpredictable and selection of influenza B seed viruses by this method can be a rate-limiting step in seasonal influenza vaccine manufacture. We recently have shown that selection of stable cold-adapted mutants from seasonal epidemic influenza B viruses is associated with improved growth. In this study, specific mutations were identified that were responsible for growth enhancement as a consequence of adaptation to growth at lower temperatures. Molecular analysis revealed that the following mutations in the HA, NP and NA genes are required for enhanced viral growth: G156/N160 in the HA, E253, G375 in the NP and T146 in the NA genes. These results demonstrate that the growth of seasonal influenza B viruses can be optimized or improved significantly by specific gene modifications.