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INFECTIOUS DISEASES

Exploring the landscape of immune responses to influenza infection and vaccination

Nature Medicine volume 28, pages 239–240 (2022)Cite this article

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The antibody landscape after H3N2 vaccination may be shaped largely by recent infections; further exploration of immune dynamics could inform influenza vaccination strategies.

Influenza viruses are susceptible to continuous antigenic drift, whereby accumulating changes in key antigenic sites (including in the hemagglutinin (HA) glycoprotein head of the virus) lead to evasion of existing antibodies. A person’s antibody landscape therefore reflects the timing of that individual’s lifetime exposures to influenza virus antigens through infection and vaccination1. H3N2 influenza viruses are particularly susceptible to antigenic drift, and data from 2010 onward suggest lower vaccine efficacy against these viruses following repeated vaccination2. Pre-existing subtype-specific immunity can influence the response to new influenza strains, which in turn influences vaccine efficacy3, and these effects are governed by the antigenic distance between consecutive seasonal strains and vaccine strains4,5. The reigning hypotheses include (but are not limited to) competition between B cell clones that leads to antigenic seniority, referred to as ‘original antigenic sin’ (an antibody imprinting effect induced by the first childhood exposure to influenza virus)6, and undesirable neutralization of vaccine antigens because of pre-existing antibodies, known as the ‘infection block hypothesis’7. However, the mechanism whereby immunity based on prior infection shapes vaccine-induced antibodies is unclear.

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Fig. 1: Map of the HA landscape to a panel of H3N2 viruses (1968–2018) in a household cohort study.

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Authors and Affiliations

  1. HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Sophie A. Valkenburg & Leo L. M. Poon

  2. Division of Public Health Laboratory Sciences, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China

    Leo L. M. Poon

  3. Centre for Immunology & Infection, Hong Kong Science Park, Hong Kong SAR, China

    Leo L. M. Poon

Authors
  1. Sophie A. Valkenburg
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  2. Leo L. M. Poon
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S.A.V. and L.L.M.P. wrote and approved the manuscript.

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Correspondence to Leo L. M. Poon.

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Competing interests

L.L.M.P. holds patents for influenza vaccines.

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Valkenburg, S.A., Poon, L.L.M. Exploring the landscape of immune responses to influenza infection and vaccination. Nat Med 28, 239–240 (2022). https://doi.org/10.1038/s41591-021-01656-4

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