Imperial College London


Faculty of MedicineSchool of Public Health

Honorary Research Fellow







Norfolk PlaceSt Mary's Campus





Publication Type

3 results found

Kucharski AJ, Gog JR, 2012, Age profile of immunity to influenza: effect of original antigenic sin., Theor Popul Biol, Vol: 81, Pages: 102-112

When multiple infections are possible during an individual's lifetime, as with influenza, a host's history of infection and immunity will determine the result of future exposures. In turn, the suite of varying individual infection histories will shape the population level dynamics of the disease. Exploring the consequences of precisely how immunity is acquired using mathematical models has proven challenging though: if n strains have circulated previously, there are 2(n) combinations of past infection to consider. However, by using an age-structured mathematical model of a disease with multiple strains, we can examine the population immune profile without explicitly keeping track of all possible infection histories. This framework allows previously unknown consequences of assumptions about immune acquisition to be observed. In particular, we see that 'original antigenic sin' can reduce immunity in some age groups: these immune blind spots could be responsible for the unexpectedly high severity of certain past influenza epidemics.

Journal article

Kucharski A, Gog JR, 2012, Influenza emergence in the face of evolutionary constraints., Proc Biol Sci, Vol: 279, Pages: 645-652

Different influenza subtypes can evolve at very different rates, but the causes are not well understood. In this paper, we explore whether differences in transmissibility between subtypes can play a role if there are fitness constraints on antigenic evolution. We investigate the problem using a mathematical model that separates the interaction of strains through cross-immunity from the process of emergence for new antigenic variants. Evolutionary constraints are also included with antigenic mutation incurring a fitness cost. We show that the transmissibility of a strain can become disproportionately important in dictating the rate of antigenic drift: strains that spread only slightly more easily can have a much higher rate of emergence. Further, we see that the effect continues when vaccination is considered; a small increase in the rate of transmission can make it much harder to control the frequency at which new strains emerge. Our results not only highlight the importance of considering both transmission and fitness constraints when modelling influenza evolution, but may also help in understanding the differences between the emergence of H1N1 and H3N2 subtypes.

Journal article

Kucharski AJ, Gog JR, 2012, The role of social contacts and original antigenic sin in shaping the age pattern of immunity to seasonal influenza., PLoS Comput Biol, Vol: 8

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.

Journal article

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