tetano
Editor, Senior Moderator
J Infect Dis
. 2026 Jan 16:jiag030.
doi: 10.1093/infdis/jiag030. Online ahead of print.
Cross-reactive H5N1 neuraminidase antibodies by age and influenza A imprinting cohorts of the past century: population-based serosurvey, British Columbia, Canada
Danuta M Skowronski[SUP] 1 [/SUP], Charlene Ranadheera[SUP] 2 [/SUP], Samantha E Kaweski[SUP] 1 [/SUP], Suzana Sabaiduc[SUP] 1 [/SUP], Lea Separovic[SUP] 1 [/SUP], Gaby Makowski[SUP] 2 [/SUP], Johnny Ung[SUP] 2 [/SUP], Romina C Reyes[SUP] 3 [/SUP], Bonnie Henry[SUP] 4 [/SUP], Arianne Albert[SUP] 5 [/SUP], Felicity Clemens[SUP] 5 [/SUP], Darwyn Kobasa[SUP] 6 [/SUP], Nathalie Bastien[SUP] 2 [/SUP]
Affiliations
Background: Pre-existing immunity to emerging influenza viruses informs pandemic risk assessment. We compared cross-reactive neuraminidase (NA) antibody levels against avian influenza A(H5N1) by age and birth (imprinting) cohorts defined by periods of human influenza A subtype (H1N1, H2N2 or H3N2) circulation over the past century.
Methods: We used anonymized, residual sera collected from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey conducted in British Columbia, Canada. We assessed NA inhibition antibody titres by enzyme-linked lectin assay against clade 2.3.4.4b H5N1, and 2009 H1N1pdm09 and 1968 H3N2 pandemic strains.
Results: Among 575 participants with median age 32 (IQR: 15-62) years, 404 (70%) had detectable anti-N1 titres >10 against H5N1, with 260 (45%), 182 (32%) and 98 (17%) having titres >40, >80 and >160, respectively. Anti-N1 titres against 2009 H1N1pdm09 and H5N1 were strongly correlated (r=0.86; 95%CI: 0.82-0.89), with both highest among young adults born 1997-2003 who were school-aged children during the 2009 H1N1 pandemic (427.9, 100.8), lowest among the youngest and least influenza-experienced pediatric cohorts born 2015-2023 (20.7, 6.8) and middle-aged adults born during the 1957-1967 H2N2 era (25.1, 10.7), thereafter increasing toward a similar secondary peak among the oldest cohorts born during the pre-1947 H1N1 era (387.3, 81.0).
Conclusions: A substantial proportion of the population has pre-existing anti-N1 against H5N1, with age-related variation reflecting H1N1 imprinting and exposure opportunities. Through heightened attack rates and shifts in immunological hierarchies, historic pandemics shape and expand the immune repertoire with implications for pre-immunity to emerging zoonotic threats.
Keywords: H5N1; age; antibody; avian; birth cohort; genomics; imprinting; influenza; neuraminidase.
. 2026 Jan 16:jiag030.
doi: 10.1093/infdis/jiag030. Online ahead of print.
Cross-reactive H5N1 neuraminidase antibodies by age and influenza A imprinting cohorts of the past century: population-based serosurvey, British Columbia, Canada
Danuta M Skowronski[SUP] 1 [/SUP], Charlene Ranadheera[SUP] 2 [/SUP], Samantha E Kaweski[SUP] 1 [/SUP], Suzana Sabaiduc[SUP] 1 [/SUP], Lea Separovic[SUP] 1 [/SUP], Gaby Makowski[SUP] 2 [/SUP], Johnny Ung[SUP] 2 [/SUP], Romina C Reyes[SUP] 3 [/SUP], Bonnie Henry[SUP] 4 [/SUP], Arianne Albert[SUP] 5 [/SUP], Felicity Clemens[SUP] 5 [/SUP], Darwyn Kobasa[SUP] 6 [/SUP], Nathalie Bastien[SUP] 2 [/SUP]
Affiliations
- PMID: 41542940
- DOI: 10.1093/infdis/jiag030
Background: Pre-existing immunity to emerging influenza viruses informs pandemic risk assessment. We compared cross-reactive neuraminidase (NA) antibody levels against avian influenza A(H5N1) by age and birth (imprinting) cohorts defined by periods of human influenza A subtype (H1N1, H2N2 or H3N2) circulation over the past century.
Methods: We used anonymized, residual sera collected from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey conducted in British Columbia, Canada. We assessed NA inhibition antibody titres by enzyme-linked lectin assay against clade 2.3.4.4b H5N1, and 2009 H1N1pdm09 and 1968 H3N2 pandemic strains.
Results: Among 575 participants with median age 32 (IQR: 15-62) years, 404 (70%) had detectable anti-N1 titres >10 against H5N1, with 260 (45%), 182 (32%) and 98 (17%) having titres >40, >80 and >160, respectively. Anti-N1 titres against 2009 H1N1pdm09 and H5N1 were strongly correlated (r=0.86; 95%CI: 0.82-0.89), with both highest among young adults born 1997-2003 who were school-aged children during the 2009 H1N1 pandemic (427.9, 100.8), lowest among the youngest and least influenza-experienced pediatric cohorts born 2015-2023 (20.7, 6.8) and middle-aged adults born during the 1957-1967 H2N2 era (25.1, 10.7), thereafter increasing toward a similar secondary peak among the oldest cohorts born during the pre-1947 H1N1 era (387.3, 81.0).
Conclusions: A substantial proportion of the population has pre-existing anti-N1 against H5N1, with age-related variation reflecting H1N1 imprinting and exposure opportunities. Through heightened attack rates and shifts in immunological hierarchies, historic pandemics shape and expand the immune repertoire with implications for pre-immunity to emerging zoonotic threats.
Keywords: H5N1; age; antibody; avian; birth cohort; genomics; imprinting; influenza; neuraminidase.