Seasonal influenza viruses cause recurring global epidemics by continually evolving to escape host immunity. The viral constraints and host immune responses that limit and drive the evolution of these viruses are increasingly well understood. However, it remains unclear how most of these advances improve the capacity to reduce the impact of seasonal influenza viruses on human health. In this Review, we synthesize recent progress made in understanding the interplay between the evolution of immunity induced by previous infections or vaccination and the evolution of seasonal influenza viruses driven by the heterogeneous accumulation of antibody-mediated immunity in humans. We discuss the functional constraints that limit the evolution of the viruses, the within-host evolutionary processes that drive the emergence of new virus variants, as well as current and prospective options for influenza virus control, including the viral and immunological barriers that must be overcome to improve the effectiveness of vaccines and antiviral drugs.
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The authors thank the European Research Council for financial support under grant no. 818353 and the Dutch Research Council (NWO) for financial support under VICI grant number 09150182010027.
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Antigenic drift
Gradual accumulation of genetic mutations in the surface glycoproteins of seasonal influenza viruses that periodically result in the emergence of a novel antigenic variant.
- Antigenic seniority
A concept in immunology in which immune responses of individuals to pathogens experienced earlier in life tend to be stronger and more long lasting than those to pathogens experienced later in life.
- Backboosting antibody response
Antibody response to infection or vaccination based on the recall of previously acquired immune memory response to a partially cross-reactive antigen or epitope.
Reduction in population size that results in a contraction in genetic diversity.
- Deep mutational scanning
An experimental method that uses high-throughput sequencing technology to measure the functional capacity of amino acid substitutions across a set of, or all, positions of a protein.
- Genome reassortment
Genomic rearrangement of two or more influenza viruses that infect the same cell by mixing their genetic segments to result in a genetically novel virus.
- Haemagglutination inhibition (HAI) assays
Experimental assays that characterize the antigenicity of viruses by measuring the ability of host serum to inhibit agglutination of red blood cells by the virus.
Describes an antigen or epitope as the preferential target of the immune system.
- Neuraminidase inhibition (NAI) assays
Experimental assays that measure the ability of host serum to block the sialidase activity of neuraminidase.
- Original antigenic sin
(OAS). Refers to the immunological imprinting of the first exposure to influenza viruses during childhood. Subsequent infections by antigenically distinct influenza viruses boost the response to epitopes shared between these viruses.
- Within-host evolution
Evolution of viruses that occurs at the level of an individual infected host.
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Han, A.X., de Jong, S.P.J. & Russell, C.A. Co-evolution of immunity and seasonal influenza viruses. Nat Rev Microbiol 21, 805–817 (2023). https://doi.org/10.1038/s41579-023-00945-8
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