Contribution of neuraminidase of influenza viruses to the sensitivity to serum inhibitors and reassortment efficiency

Abstract

Live attenuated influenza vaccine (LAIV) consists of reassortant viruses with hemagglutinin (HA) and neuraminidase (NA) gene segments inherited from the circulating wild-type (WT) parental viruses and six internal protein-encoding gene segments from cold-adapted attenuated master donor viruses (genome composition 6 : 2). In this study, we describe the difficulties in development of LAIV strains depending on the phenotypic peculiarities of the WT viruses used for reassortment. Genomic-composition analysis of 849 reassortants revealed that over 80% of reassortants based on the inhibitor-resistant WT viruses inherited WT NA as compared to 26% of reassortants based on the inhibitor-sensitive WT viruses. In addition, the highest percentage of vaccine genotype reassortants was achieved when WT parental viruses were resistant to nonspecific serum inhibitors. We show that NA may play a role in the influenza virus’ sensitivity to a nonspecific serum inhibitors. Replacing the NA of the inhibitor-sensitive WT virus with the NA of the inhibitor-resistant master donor virus significantly decreased the sensitivity of the resulting reassortant virus to nonspecific inhibitors.