Immune imprinting in early life shapes cross-reactivity to influenza B virus haemagglutinin

Peta Edler; Lara S U Schwab; Malet Aban; Michelle Wille; Natalie Spirason; Yi-Mo Deng; Michael A Carlock; Ted M Ross; Jennifer A Juno; Steve Rockman; Adam K Wheatley; Stephen J Kent; Ian G Barr; David J Price; Marios Koutsakos

doi:10.1038/s41564-024-01732-8

Immune imprinting in early life shapes cross-reactivity to influenza B virus haemagglutinin

Nat Microbiol. 2024 Aug;9(8):2073-2083. doi: 10.1038/s41564-024-01732-8. Epub 2024 Jun 18.

Authors

Peta Edler¹, Lara S U Schwab², Malet Aban³, Michelle Wille^{3

4}, Natalie Spirason³, Yi-Mo Deng³, Michael A Carlock^{5

6

7}, Ted M Ross^{5

6

7

8}, Jennifer A Juno², Steve Rockman^{2

9}, Adam K Wheatley², Stephen J Kent^{2

10}, Ian G Barr^{2

3}, David J Price^{1

11}, Marios Koutsakos¹²

Affiliations

¹ Department of Infectious Diseases, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
² Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
³ WHO Collaborating Centre for Reference and Research on Influenza, Royal Melbourne Hospital, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
⁴ Centre for Pathogen Genomics, University of Melbourne, Melbourne, Victoria, Australia.
⁵ Center for Vaccines and Immunology, University of Georgia, Athens, GA, USA.
⁶ Department of Infectious Diseases, University of Georgia, Athens, GA, USA.
⁷ Florida Research and Innovation Centre, Cleveland Clinic, Port Saint Lucie, FL, USA.
⁸ Department of Infection Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
⁹ Vaccine Product Development, CSL Seqirus Ltd, Parkville, Victoria, Australia.
¹⁰ Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
¹¹ Centre for Epidemiology & Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
¹² Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia. [email protected].

PMID: 38890491
DOI: 10.1038/s41564-024-01732-8

Abstract

Influenza exposures early in life are believed to shape future susceptibility to influenza infections by imprinting immunological biases that affect cross-reactivity to future influenza viruses. However, direct serological evidence linked to susceptibility is limited. Here we analysed haemagglutination-inhibition titres in 1,451 cross-sectional samples collected between 1992 and 2020, from individuals born between 1917 and 2008, against influenza B virus (IBV) isolates from 1940 to 2021. We included testing of 'future' isolates that circulated after sample collection. We show that immunological biases are conferred by early life IBV infection and result in lineage-specific cross-reactivity of a birth cohort towards future IBV isolates. This translates into differential estimates of susceptibility between birth cohorts towards the B/Yamagata and B/Victoria lineages, predicting lineage-specific birth-cohort distributions of observed medically attended IBV infections. Our data suggest that immunological measurements of imprinting could be important in modelling and predicting virus epidemiology.

MeSH terms

Adult
Antibodies, Viral* / blood
Antibodies, Viral* / immunology
Birth Cohort
Cross Reactions* / immunology
Cross-Sectional Studies
Disease Susceptibility / immunology
Female
Hemagglutination Inhibition Tests
Hemagglutinin Glycoproteins, Influenza Virus / immunology
Humans
Influenza B virus* / immunology
Influenza, Human* / immunology
Influenza, Human* / virology
Male
Middle Aged

Substances

Antibodies, Viral
Hemagglutinin Glycoproteins, Influenza Virus