A systematic approach to vaccine complexity using an automaton model of the cellular and humoral immune systemI. Viral characteristics and polarized responses

Abstract

A modern approach to vaccination faces the compound complexity of microorganism behavior and immune response triggering and regulation. Since computational modeling can yield useful guidelines for biological experimentation, we have used IMMSIM3, a cellular automaton model for simulating humoral- and cell-mediated responses, to explore a wide range of virus-host relations. Sixty-four virtual viruses were generated by an assortment of speed of growth, infectivity level and lethal load. The outcome of the infections, as influenced by the immune response and the bolstering of cures, obtained by vaccine presensitization are illustrated in this first article. The results of the in machina experiments allow us to relate the success rate of responses to certain combinations of viral parameters and by freezing one or the other branch, and to determine that some viruses are more susceptible to humoral, and others to cellular responses, depending either on single parameters or combinations thereof. This finding allows prediction of which infection may be susceptible to polarized ((Th)1>Th2 and Th1<Th2) responses and will eventually help designing vaccines whose action relies on antagonizing both the specificity and the behavior of the invader. A second, not lesser, result of this study is the finding that humoral and cellular responses, while cooperating, towards the cure of the infected body, also show significant patterns of competition and mutual thwarting. Copyright (C) 2000 Elsevier Science Ltd.