Immunomodulator plasmid projected by systems biology as a candidate for the development of adjunctive therapy for respiratory syncytial virus infection

Abstract An imbalance in Th1/Th2 cytokine immune response has been described to influence the pathogenesis of respiratory syncytial virus (RSV) acute bronchiolitis and the severity of infection. Th2-driven response has been well described under first RSV vaccine (formalin-inactivated RSV vaccine antigens) and replicated in some conditions for RSV-infected mice, in which a Th2-dependent lung eosinophilia increases illness severity, accompanied of tissue damage. Currently, several prototypes of RSV vaccine are being tested, but there is no vaccine available so far. The advance of bioinformatics can help to solve this issue. Systems biology approaches based on network topological analysis may help to identify new genes in order to direct Th1 immune response during RSV challenge. For this purpose, network centrality analyses from high-throughput experiments were performed in order to select major genes enrolled in each T-helper immune response. Thus, genes termed Hub (B) and bottlenecks (H), which control the flow of biological information (Th1 or Th2 immune response, in this case) within the network, would be identified. As these genes possess high potential to promote Th1 immune response, they could be cloned under regulation of specific promoters in a plasmid, which will be available as a gene-transfer adjunctive to vaccines. Th1 immune response potentiated by our strategy may contribute to accelerate Th1/Th2 shift from neonatal immune system, which might favor protective immunity against RSV infection and reduce lung damage.