Cross-reactive #neuraminidase inhibition #antibodies against #H5N1 by consecutive #influenza A imprinting cohorts of the past century: population-based serosurvey, British Columbia, #Canada

 

Abstract

Background: 

Avian influenza of the H5N1 subtype shares substantial relatedness in its neuraminidase (NA) surface protein with human influenza A H1N1 viruses of the past century. Understanding variation in pre-existing anti-N1 antibodies against H5N1 is critical to pandemic risk assessment and preparedness. 

Methods: 

We used anonymized, residual sera collected equally from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey in British Columbia, Canada. We assessed NA inhibition antibody titres by enzyme-linked lectin assay against H5N1 (N=575), H1N1pdm09 (N=250) and H3N2 (N=205). We compared anti-NA titres by birth (imprinting) cohorts defined in relation to historic N1 and/or N2 exposure opportunities. 

Results: 

Among participants with median age 32 (IQR: 15-62) years, 404 (70%) had cross-reactive anti-N1 titre ≥10 against H5N1, with 260 (45%), 182 (32%) and 98 (17%), having titres ≥40, ≥80 and ≥160, respectively. H5N1 titres were consistently lower but strongly associated with H1N1pdm09 (r=0.86; 95%CI:0.82-0.89). Geometric mean titres against H1N1pdm09 and H5N1 peaked among young adults born 1997-2003 (427.9, 100.8), declining to lows among young children born 2015-2023 (20.7, 6.8) and middle-aged adults born 1957-1967 (25.1, 10.7), increasing to similar secondary peak among older adults born pre-1947 (387.3, 81.0). 

Conclusions: 

A substantial proportion of the population has pre-existing, cross-reactive anti-N1 antibodies against H5N1. We interpret variation by age and imprinting cohorts within a unifying hypothesis, emphasizing the role of historic influenza pandemics in expanding and refining the immune repertoire through heightened attack rates and shifts in immunological hierarchies. Our findings have implications for H5N1 and other zoonotic influenza risk assessment.

Competing Interest Statement

DMS is Principal Investigator on grants received to her institution from the Public Health Agency of Canada, Pacific Public Health Foundation, Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research for unrelated work. As the Provincial Health Officer with authority under the emergency provisions of the Public Health Act, BH authorized the provision and analysis of the anonymized sera used in this study; the study was separately reviewed and approved by the UBC Clinical Research Ethics Board and Health Canada-Public Health Agency of Canada Research Ethics Board. No other competing interests were declared.

Funding Statement

This work was supported by the Public Health Agency of Canada (Grant number: 2021-HQ-00067), received by the Institution of DMS. The views expressed herein do not necessarily represent the views of the Public Health Agency of Canada.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.09.19.25336209v1

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