Mapping the Antibody Repertoires in Ferrets with Repeated Influenza A/H3 Infections: Is Original Antigenic Sin Really “Sinful”?

Abstract

The influenza-specific antibody repertoire is continuously reshaped by infection and vaccination. The host immune response to contemporary viruses can be redirected to preferentially boost antibodies specific for viruses encountered early in life, a phenomenon called original antigenic sin (OAS) that is suggested to be responsible for diminished vaccine effectiveness after repeated vaccination. In this study, we used a new computational tool called Neutralization Map to determine the hemagglutination inhibition profiles of individual antibodies within ferret antisera elicited by repeated influenza A/H3 infections. Our results suggest that repeated infections continuously reshape the ferret antibody repertoire, but that a broadly neutralizing antibody signature can nevertheless be induced irrespective of OAS. Overall, our study offers a new way to visualize how immune history shapes individual antibodies within a repertoire, which may help inform future vaccine design.