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

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

Although very few genomic studies have been performed in the field of vaccination it has been anticipated that the biological network concept would be useful. In this way, Poland et al. (44) proposed "the immuneresponse network theory", whereby the response to the vaccine can be viewed as the cumulative result of gene interactions. The findings in naturally infected individuals and in mouse models of infectious diseases support this hypothesis. This urges the effort to perform genome-wide studies in vaccinated mice and humans, and to compare the results with those obtained in natural infections. The same authors have suggested that the network combined with individual genomic profiles may lead to predicting the response to vaccination. This is a big challenge because it will require biological networks that capture all the relevant information, including the effect of genetic and other biological information (age, gender, etc.). This further implies that one would be able to predict the effect of single or combined perturbations such as polymorphisms on molecular phenotypes (Figure 2 ). For this pur-pose, regulatory network modeling methods would be useful: models constructed on available data to predict molecular and cellular phenotypes will provide working hypotheses that can be tested, leading to the improvement of the initial model. Interestingly, immune response system-level tools have been made available (66) . Thus, Systems Biology is a new rational approach that gives a more comprehensive understanding of networks or interacting components in the immune response to pathogen antigens. This concept has been recently reviewed (67) . It can be applied to identify signatures of protection that would be evaluated in the de- Vaccinomics) . This emergent research strategy in vaccine development was already applied to identify signatures of protection to influenza (68) and yellow fever vaccines (69) . Nevertheless, the current tools can manage small biological networks; the challenge is to develop new approaches that allow the modeling of large regulatory networks.