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

Abstract

A(H1N1) strains of Influenzavirus were responsible for 2 pandemics in the last 100 years. Because infections experienced early in life may have a long-lasting influence on future immune response against other influenza strains, we drew on previously collected seroincidence data from Singapore (n = 2,554; June–October 2009) to investigate whether the 1918 pandemic influenza 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 (born in 1911–1926) had the highest titers, followed by the youngest (born in 1987–1992). Differential response by vaccination history was also observed, with seasonal influenza vaccine being 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 a titer-mediated effect by the vaccine could, on its own, account for a negative association with seroconversion equivalent to a risk reduction of 23% (relative risk = 0.77, 95% confidence interval: 0.60, 0.99) in the oldest birth cohort. A subset of 503 samples tested against the A/Brisbane/59/2007(H1N1) and A/Puerto Rico/8/1934(H1N1) strains also revealed different age-related antibody profiles. The effectiveness of seasonal influenza vaccines against future pandemic strains could thus be age-dependent and related to early-life exposures.

Comparative review of respiratory diseases caused by coronaviruses and influenza A viruses during epidemic season

“…It was noticed that the virus caused more deaths in people who are younger than 65 [36]. Some scientists deduced that the senior people may carry the immune memories from those induced by 1918H1N1-like flu viruses in their early years, which cross protected them from the H1N1pdm09 virus attack [37]. However, the fact is that the 1918H1N1 virus also caused more deaths in younger people [38].…”

The 1918 Influenza Pandemic: Looking Back, Looking Forward

“…Chuah et al ( 9 ) used seroepidemiology and structural equation modeling to answer the inverse question: How did early-life exposure to the 1918 pandemic virus impact how people responded to the 2009 pandemic, which was caused by an antigenically similar virus? They found evidence for immunologic priming from the 1918 virus in the oldest people they studied (individuals 80 years of age or older) that impacted both baseline titers and vaccine response in 2009.…”

“…Information about global connectivity in the 19th century is tenuous, and influenza records before 1890 are scarce. Epidemiologic reconstructions of “modern” pandemics of the type presented here ( 6 – 9 ) provide indirect information on the exposures of populations that are now long gone, generating valuable hypotheses about influenza circulation patterns and disease dynamics well into the 19th century. Such reconstructions offer precious insights into what influenza may have looked like 200 years ago in a very different world and how long-term changes in human demography and mobility may affect disease dynamics ( 22 ).…”

“…We are just beginning to scratch the surface of the intricate relationship between the influenza virus and the complex immune history of a host who has had repeated influenza exposures ( 9 , 18 – 20 , 28 ). It is unclear whether we will be able to fully understand these interactions in the foreseeable future; in the meantime, population birth cohorts carrying important influenza immune histories disappear.…”

“…In commemoration of the centennial of the 1918 pandemic, the American Journal of Epidemiology has convened a collection of 12 articles that further illuminate the epidemiology of that pandemic and consider whether we would be more prepared if an equally deadly influenza virus were to emerge today. Five of the 12 articles touch on the origins of the 1918 pandemic virus, addressing the role of swine as mixing vessels in this and other pandemic events ( 5 ), the age-specific mortality patterns of the pandemic ( 6 – 8 ), and prior population immunity ( 9 ). Others include reports on geographic and social heterogeneities in the pandemic experience in which the authors describe the spatial diffusion of the pandemic in India and Portugal ( 10 , 11 ), the socioeconomic predictors of high mortality risk in Sweden and globally ( 12 , 13 ), and the consequences of the pandemic on US natality rates ( 14 , 15 ).…”