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

doi:10.3390/v15020374

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

Viruses. 2023 Jan 28;15(2):374. doi: 10.3390/v15020374.

Authors

Tal Einav¹, Martina Kosikova², Peter Radvak², Yuan-Chia Kuo², Hyung Joon Kwon², Hang Xie²

Affiliations

¹ Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
² 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.

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 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.

Keywords: broadly neutralizing antibody; immune imprinting; influenza A H3N2 virus; mapping antibody repertoires; original antigenic sin; repeated influenza exposures.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Antibodies
Broadly Neutralizing Antibodies
Ferrets
Humans
Influenza Vaccines*
Influenza, Human*

Substances

Antibodies
Influenza Vaccines
Broadly Neutralizing Antibodies

Grants and funding

This work was supported in part by the intramural research fund of the Center for Biologics Evaluation and Research, US Food and Drug Administration (to H.X.). Tal Einav is a Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation (DRQ 01-20).