Figure 3: Evolution of vaccine development during the last 30 years.

In the 1980s discovery was the major obstacle to vaccine development. The limited technologies available allowed the development of killed, live-attenuated, toxoid, or polysaccharide vaccines only. Development used to be fast with registration requiring a few hundred subjects in clinical trials. During the 1990s, recombinant DNA technologies, conjugation and the availability of the genome sequences allowed the acceleration of the discovery phase and subsequently the discovery of vaccines against diseases that were previously impossible. High-throughput methods allowed parallel testing of multiple approaches, markedly shortening the identification of the best candidate vaccines and formulations. However, development timelines and budgets have expanded. The number of subjects required today to test safety and immunogenicity in phase I clinical trials, and in phase II studies required to define the most promising vaccine candidate, is larger than the number required to license a vaccine in 1980. Furthermore, the number of subjects required to establish safety and efficacy in phase III field registration trials has grown beyond reasonable proportions and today the licensing of a new vaccine may require up to 80,000 people in clinical trials. If phase I, II and III studies are performed sequentially, any new vaccine starting phase I requires 10 years for clinical testing. The bottom section of the figure illustrates our expectation that systems biology and adaptive design of clinical trials will accelerate the vaccine development timelines. Multiple phase I/II clinical trials can be started in parallel and be intensively and systematically monitored by systems biology until the most promising candidate emerges. At this point the arm of the most promising candidate is expanded into a phase III registration trial, saving time compared to the sequential approach. Adapted from ref. 58.

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