Abstract
Recent serological studies of seasonal influenza A in humans suggest a striking characteristic profile of immunity against age, which holds across different countries and against different subtypes of influenza. For both H1N1 and H3N2, the proportion of the population seropositive to recently circulated strains peaks in school-age children, reaches a minimum between ages 35–65, then rises again in the older ages. This pattern is little understood. Variable mixing between different age classes can have a profound effect on disease dynamics, and is hence the obvious candidate explanation for the profile, but using a mathematical model of multiple influenza strains, we see that age dependent transmission based on mixing data from social contact surveys cannot on its own explain the observed pattern. Instead, the number of seropositive individuals in a population may be a consequence of ‘original antigenic sin’; if the first infection of a lifetime dominates subsequent immune responses, we demonstrate that it is possible to reproduce the observed relationship between age and seroprevalence. We propose a candidate mechanism for this relationship, by which original antigenic sin, along with antigenic drift and vaccination, results in the age profile of immunity seen in empirical studies.
Highlights
Influenza A evolves over time, escaping the immunity of human host populations [1]
Age-specific immunity has been widely discussed for the 2009 influenza pandemic, the age profile of immunity to seasonal influenza remains little understood
Our results suggest that rather than variable mixing between different age groups being solely responsible, the pattern may be shaped by an effect known as ‘original antigenic sin’, by which the first infection of a lifetime dictates subsequent immune responses: instead of developing antibodies to every new virus that is encountered, the immune system may reuse the response to a similar virus it has already seen
Summary
Influenza A evolves over time, escaping the immunity of human host populations [1]. As a result, individuals are exposed to a range of different strains over a lifetime, and different age groups have varying levels of antibodies to particular strains, depending on which viruses they have seen. Several serological studies during the 2009 influenza pandemic considered recent seasonal H1N1 and H3N2 strains, with haemagglutination-inhibition (HI) titres given for different age groups. Across a number of countries, the data all follow a distinct pattern [2,3,4,5,6,7,8]: a high proportion of individuals are seropositive (HI titre.40) in adolescence, followed by a clear decrease in seropositivity between adolescence and age 60–65, before a rise in the older ages. Despite the increasingly availability of social contact data [12,13], it has previously been difficult to compare mathematical model outputs with data from serological studies for seasonal influenza: the proliferation of variables required as the number of strains in the model increases makes it technically challenging to look at the long term impact of different assumptions
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