Clinical vaccine development

Han, Seunghoon

In the traditional paradigm, disease caused by vaccination has been a serious problem [27] . Rappuoli [28] has stressed the methodological approaches used to overcome the risks of vaccination in the 21st century (Table 3 ). In addition, thanks to improvements in genomic techniques, new vaccine-design methods, such as reverse vaccinology [29] , have enabled the high-throughput screening of vaccine candidates with greater confidence in their safety profiles. The characteristics Table 3 . New strategies for improving vaccine safety Screening for sequences homologous to proteins encoded by the human genome to remove sequences mimicking self-antigens Immunohistochemistry to check cross-reactions with human tissues Multiple cytokine induction to profile the Th1/Th2 immune response and the potential for autoimmunity Availability of well-controlled cell lines to avoid the use of whole animals (smallpox) and primary monkey kidney cells (polio Sabin), which may induce autoimmunity or contain undefined viral/prion contaminants Control of cell lines for prion proteins Simulation of immune response data from different immunization regimens Mathematical models of disease, biomarkers, immune response kinetics, efficacy, and safety Mouse-human crossover studies to understand the role of Toll-like receptors (TLRs) Animal and in vitro models to test disease enhancement (RSV, influenza, and measles) Large Phase III and Phase IV studies to exclude statistically rare events of vaccine recipients are also considered, and there is much focus on developing ways to personalize vaccination, which is termed 'vaccinomics' [30] .