Asynchrony between virus diversity and antibody selection limits influenza virus evolution

Author:

Morris Dylan H1ORCID,Petrova Velislava N2,Rossine Fernando W1,Parker Edyth34ORCID,Grenfell Bryan T15ORCID,Neher Richard A6ORCID,Levin Simon A1,Russell Colin A4ORCID

Affiliation:

1. Department of Ecology & Evolutionary Biology, Princeton University, Princeton, United States

2. Department of Human Genetics, Wellcome Trust Sanger Institute, Cambridge, United Kingdom

3. Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom

4. Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands

5. Fogarty International Center, National Institutes of Health, Bethesda, United States

6. Biozentrum, University of Basel, Basel, Switzerland

Abstract

Seasonal influenza viruses create a persistent global disease burden by evolving to escape immunity induced by prior infections and vaccinations. New antigenic variants have a substantial selective advantage at the population level, but these variants are rarely selected within-host, even in previously immune individuals. Using a mathematical model, we show that the temporal asynchrony between within-host virus exponential growth and antibody-mediated selection could limit within-host antigenic evolution. If selection for new antigenic variants acts principally at the point of initial virus inoculation, where small virus populations encounter well-matched mucosal antibodies in previously-infected individuals, there can exist protection against reinfection that does not regularly produce observable new antigenic variants within individual infected hosts. Our results provide a theoretical explanation for how virus antigenic evolution can be highly selective at the global level but nearly neutral within-host. They also suggest new avenues for improving influenza control.

Funder

H2020 European Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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