The use of genomics in microbial vaccine development

Abstract

Vaccination is one of the most effective tools for the prevention of infectious diseases. The availability of complete genome sequences, together with the progression of high-throughput technologies such as functional and structural genomics, has led to a new paradigm in vaccine development. Pan-genomic reverse vaccinology, with the comparison of sequence data from multiple isolates of the same species of a pathogen, increases the opportunity of the identification of novel vaccine candidates. Overall, the conventional empiric approach to vaccine development is being replaced by vaccine design. The recent development of synthetic genomics may provide a further opportunity to design vaccines.

Figure 1

The impact of genomics in vaccine discovery research and development. In the past, the conventional vaccine discovery approaches were time-consuming and the identification of protective antigens took years or decades. The genomics advent in the 1990s, with the availability of whole-genome sequences and high-throughput technologies, and the progress in immunology have provided novel strategies for a more rapid (one to two years) identification of antigens, dramatically decreasing the time for discovery research and vaccine development. Following stages of development and manufacture until vaccine launch could, however, become more complex in the near future, resulting from the emergence of new infectious diseases and the largest request of more safe, effective and cheap vaccines. Major challenges still remain in optimizing the commercial aspect of vaccine development, due mainly to increasingly stringent regulatory requirements, to economic limits, to the need of increasing global priority attributed to vaccination and to other socioeconomic issues.

Figure 2

Schematic image of the main -omics fields and their applications in vaccine discovery research and development. The availability of complete pathogen genome sequences, with the contemporary development of bioinformatics tools, has led to a new paradigm of the vaccine development. The whole-genome sequence accessibility allowed the advent of the classical and, more recently, the pan-genomic reverse vaccinology, which are supported by molecular epidemiology studies for the selection of strains representative of a given pathogen. Functional (transcriptomics and proteomics) genomics are playing a central role in the understanding of host–pathogen interaction. Structural genomics, with the atomic resolution of the structure, could provide the basis for the rational engineering of potential antigens. Moreover, in very recent times, we are attending to the development of synthetic genomics. All these areas can contribute and/or have the potential to favor the development of the so-called third-generation vaccines, through the selection or design of promising vaccine candidates to take forward into clinical trials.