A systematic approach to vaccine complexity using an automaton model of the cellular and humoral immune system I. Viral characteristics and polarizedresponses

A modern approach to vaccination faces the compound complexity of microorga nism behavior and immune response triggering and regulation. Since computat ional modeling can yield useful guidelines for biological experimentation, we have used IMMSIM3, a cellular automaton model for simulating humoral- an d cell-mediated responses, to explore a wide range of virus-host relations. Sixty-four virtual viruses were generated by an assortment of speed of gro wth, infectivity level and lethal load. The outcome of the infections, as i nfluenced by the immune response and the bolstering of cures, obtained by v accine presensitization are illustrated in this first article. The results of the in machina experiments allow us to relate the success rate of respon ses to certain combinations of viral parameters and by freezing one or the other branch, and to determine that some viruses are more susceptible to hu moral, and others to cellular responses, depending either on single paramet ers or combinations thereof. This finding allows prediction of which infect ion may be susceptible to polarized ((Th)(1) > Th-2 and Th-1 < Th-2) respon ses and will eventually help designing vaccines whose action relies on anta gonizing both the specificity and the behavior of the invader. A second, no t lesser, result of this study is the finding that humoral and cellular res ponses, while cooperating, towards the cure of the infected body, also show significant patterns of competition and mutual thwarting. (C) 2000 Elsevie r Science Ltd. All rights reserved.