Contribution of Neuraminidase to the Efficacy of Seasonal Split Influenza Vaccines in the Ferret Model
Miruna E. Rosu, Adinda Kok, Theo M. Bestebroer, Dennis de Meulder, Elwin P. Verveer, Mark Pronk, Lennard J. M. Dekker, Theo M. Luider, Mathilde Richard, Judith M. A. van den Brand, Ron A. M. Fouchier, Sander Herfst
Abstract
Despite the availability of vaccines, influenza virus infections continue to cause substantial morbidity and mortality in humans. Currently available influenza vaccines take primarily the hemagglutinin (HA) into account, but the highly variable nature of this protein as a result of antigenic drift has led to a recurrent decline in vaccine effectiveness. While the protective effect of neuraminidase (NA) antibodies has been highlighted by several studies, there are no requirements with regard to quantity or quality of NA in licensed vaccines, and NA immunity remains largely unexploited. Since antigenic changes in HA and NA are thought to occur asynchronously, NA immunity could compensate for reduced vaccine efficacy when drift in HA occurs. By matching and mismatching the HA and NA components of monovalent split inactivated vaccines, we demonstrated the potential of NA immunity to protect against disease, virus replication in the lower respiratory tract, and virus shedding in the ferret model.