Coping with genetic diversity: the contribution of pathogen and human genomics to modern vaccinology

Lemaire, D.; Barbosa, T.; Rihet, P.

There is accumulating evidence for a genetic control of infectious diseases. Rare primary immunodeficiencies have been shown to cause susceptibility to either multiple infectious agents or to a single type of infectious agent; these are very rare and Mendelian inherited. Twin studies have provided further evidence of a genetic control, and complex segregation analyses that explicitly model the effect of genes and the environment have revealed either multigenic predisposition or a genetic predisposition based on major genes having a big influence on the phenotypes related to the disease (22) . Several candidate genes have been associated with infectious diseases (23) . The candidate gene approach further supports the role of human genetics in resistance or susceptibility to infectious diseases. More recently, RNA interference has been used to exploit human cell models of infection with various agents to elucidate pathogen virulence mechanisms capable of subverting host pathways involved in immune regulation and pathogen killing response (24) , an approach that can be used to discover and associate differences in preferential immunoregulatory networks involved in host-pathogen interactions in susceptible versus resistant hosts. These approaches are, however, restricted to well-known genes.