Mapping the Antibody Repertoires in Ferrets with Repeated Influenza A/H3 Infections: Is Original Antigenic Sin Really “Sinful”?
Tal Einav,
Martina Kosikova,
Peter Radvak,
Yuan-Chia Kuo,
Hyung Joon Kwon,
Hang Xie
Affiliations
Tal Einav
Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
Martina Kosikova
Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, USA
Peter Radvak
Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, USA
Yuan-Chia Kuo
Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, USA
Hyung Joon Kwon
Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, USA
Hang Xie
Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993, USA
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 seasonal vaccination. Using a new computational tool called Neutralization Landscapes, we tracked the progression of hemagglutination inhibition antibodies within ferret antisera elicited by repeated influenza A/H3 infections and deciphered the influence of prior exposures on the de novo antibody response to evolved viruses. The results indicate that a broadly neutralizing antibody signature can nevertheless be induced by repeated exposures despite OAS induction. Our study offers a new way to visualize how immune history shapes individual antibodies within a repertoire, which may help to inform future universal influenza vaccine design.
