ANTIGENIC VARIATION AND THE WITHIN-HOST DYNAMICS OF PARASITES

Many parasites exhibit antigenic variation within their hosts, We use mathematical models to investigate the dynamical interaction between a n antigenically varying parasite and the host's immune system, The mod els incorporate antigenic variation in the parasite population and the generation of immune responses directed against (i) antigens specific to individual parasite variants and (ii) antigens common to all the p arasite variants, Analysis of the models allows us to evaluate the rel ative importance of variant-specific and cross-reactive immune respons es in controlling the parasite, Early in the course of infection withi n the host, when parasite diversity is below a defined threshold value (the value is determined by the biological properties of the parasite and of the host's Immune response), the variant-specific immune respo nses are predominant, Later, when the parasite diversity Is high, the cross-reactive immune response is largely responsible for controlling the parasitemia. It Is argued that Increasing antigenic diversity lead s to a switch from variant-specific to cross-reactive immune responses , These simple models mimic various features of observed infections re corded in the experimental literature, including an initial peak in pa rasitemia, a long and variable duration of infection with fluctuating parasitemia that ends with either the clearance of the parasite or per sistent infection.