Earliest infections predict the age distribution of seasonal influenza A cases

Abstract

<jats:p>Seasonal variation in the age distribution of influenza A cases suggests that factors other than age shape susceptibility to medically attended infection. We ask whether these differences can be partly explained by protection conferred by childhood influenza infection, which has lasting impacts on immune responses to influenza and protection against new influenza A subtypes (phenomena known as original antigenic sin and immune imprinting). Fitting a statistical model to data from studies of influenza vaccine effectiveness (VE), we find that primary infection appears to reduce the risk of medically attended infection with that subtype throughout life. This effect is stronger for H1N1 compared to H3N2. Additionally, we find evidence that VE varies with both age and birth year, suggesting that VE is sensitive to early exposures. Our findings may improve estimates of age-specific risk and VE in similarly vaccinated populations and thus improve forecasting and vaccination strategies to combat seasonal influenza.</jats:p>

Original Antigenic Sin: How Original? How Sinful?

“…Individuals first exposed as children to group 1 HA (H1 or H2) human viruses were preferentially protected against lethality from an avian group 1 HA virus (H5), whereas those initially exposed to a human group 2 HA virus (H3) were protected from an avian group 2 (H7) virus. Lifelong HA/NA subtype-specific susceptibility to severe infection resulting from first exposure(s) to viruses of the opposite subtype also appears to extend to H1N1 and H3N2 viruses (Arevalo et al 2019;Gostic et al 2019).…”

“…This important study hammers home the message that OAS phenotype Abs induced by vaccination can be biologically important on their own, and further, that under many circumstances they will be accompanied by primary Abs induced by the vaccine that will also be protective. At the same time, it is important to consider that there is solid evidence in animal models (Kim et al 2009), and indeed in man (Gostic et al 2016(Gostic et al , 2019Arevalo et al 2019), that priming can weaken protection afforded by subsequent infection/vaccination with other IAVs.…”

“…How important is imprinting in IAV pathogenesis and how can it be modulated? Epidemiological studies clearly show that initial exposure to IAV improves the clinical outcome decades in the future to infection with strains that possess HA from the same group (Gostic et al 2016(Gostic et al , 2019Arevalo et al 2019). To what extent is this a positive effect on homotypic immunity versus a negative effect on heterotypic immunity and are there any effects on infection with influenza B viruses or even more distantly related viruses?…”

Beyond clinical trials: Evolutionary and epidemiological considerations for development of a universal influenza vaccine

“…Another question of interest is whether HA imprinting is stronger for group 1 or group 2 viruses. A number of studies have started to confront these immunologic scenarios by analyzing influenza surveillance data stratified by birth year and virus subtype [52,53]. The early life influenza exposure of each birth cohort is reconstructed probabilistically, based on information on influenza circulation since 1918.…”

“…Recent analyses of the risk of seasonal influenza infection have illuminated the role of birth year imprinting at the HA and NA subtype levels [52,53] (Fig 2C). Those primed by H1N1 (born before 1957) experience partial protection against all seasonal influenza H1N1 viruses throughout life but no advantage against H3N2 infections.…”