Investigating the Legacy of 1918 Pandemic on Age-Related Sero-Epidemiology and Immune Responses to Subsequent Influenza A(H1N1) Viruses Through a Structural Equation Model

Abstract

Influenza A(H1N1) strains were responsible for two pandemics in the last century. As infections early in life may have long-lasting influence on future immune response against other influenza strains, we drew on previously collected sero-incidence data (n = 2554) to investigate if the 1918 pandemic virus and its early descendants produced an age-related signature in immune responses against the A/California/7/2009(H1N1)pdm09 virus of 2009. Hemagglutination inhibition assays revealed a J-shaped relationship; the oldest birth cohort (years 1911 – 1926) had the highest titers followed by the youngest (years 1987 – 1992). Differential response by vaccination history was also observed, with seasonal influenza vaccine associated with higher titers mainly in the oldest birth cohort. On the assumption that antibody titers are a correlate of protection, structural equation modeling predicted that titer-mediated effect by the vaccine could on its own account for a negative association with seroconversion equivalent to a relative risk reduction of 0.77 (95% confidence interval: 0.60, 0.99) in the oldest birth cohort (years 1911 – 1926). A subset of 503 samples tested against A/Brisbane/59/2007(H1N1) and A/Puerto Rico/8/1934(H1N1) also revealed different age-related antibody profiles. Effectiveness of seasonal influenza vaccines against future pandemic strains could thus be age-dependent and related to early life exposures.