Vaccine-Associated Enhanced Respiratory Disease following Influenza Virus Infection in Ferrets Recapitulates the Model in Pigs
J. Brian Kimble, Meghan Wymore Brand, Bryan S. Kaplan, Phillip Gauger, Elizabeth M. Coyle, Katarina Chilcote, Surender Khurana, Amy L. Vincent
Abstract
We demonstrated the susceptibility of ferrets, a laboratory model species for human influenza A virus research, to vaccine-associated enhanced respiratory disease (VAERD) using an experimental model previously demonstrated in pigs. Ferrets developed clinical characteristics of VAERD very similar to that in pigs. The hemagglutinin (HA) stalk is a potential vaccine target to develop more efficacious, broadly reactive influenza vaccine platforms and strategies. However, non-neutralizing antibodies directed toward a conserved epitope on the HA stalk induced by an oil-in-water, adjuvanted, whole influenza virus vaccine were previously shown in VAERD-affected pigs and were also identified here in VAERD-affected ferrets. The induction of VAERD in ferrets highlights the potential risk of mismatched influenza vaccines for humans and the need to consider VAERD when designing and evaluating vaccine strategies.