Current Challenges in Vaccinology

Abstract

The development of vaccines, which prime the immune system to respond to future infections, has led to global declines in morbidity and mortality from dreadful infectious communicable diseases. However, many pathogens of public health importance are highly complex and/or rapidly evolving, posing unique challenges to vaccine development. Several of these challenges include an incomplete understanding of how immunity develops, host and pathogen genetic variability, and an increased societal skepticism regarding vaccine safety. In particular, new high-dimensional omics technologies, aided by bioinformatics, are driving new vaccine development (vaccinomics). Informed by recent insights into pathogen biology, host genetic diversity, and immunology, the increasing use of genomic approaches is leading to new models and understanding of host immune system responses that may provide solutions in the rapid development of novel vaccine candidates.

Keywords: genetics; genomics; transcriptomics; vaccine; vaccine development.

Figure 1

Barriers to vaccine development. Vaccines are the most effective public health tool for controlling infectious diseases. Despite considerable success, there is room for improvement in many current vaccines and there are a large number of new and re-emerging pathogens for which we do not have effective vaccines. Vaccine development faces a number of challenges, many of which are presented here. Developing vaccines to combat current and future pathogens will require us to overcome those challenges and recent developments in genomic technologies may provide the solutions that we need.

Figure 2

The use of vaccinomics in new vaccine development. A wide array of genomic tools and techniques are available for researchers to study various aspects of pathogen biology and host physiology and immune response. Vaccinomics and similar approaches represent toolboxes that contain a specific assortment of laboratory assays, statistical analysis routines, bioinformatic methods, and computational models that can be used to generate an appropriate dataset and extract biologically meaningful results from the data. GWAS, genome wide association study; bnAbs, broadly neutralizing antibodies.

Figure 3

Contribution of genomics to vaccine development stages. The results generated by genomic approaches inform each stage of vaccine development. Initial genomics work plays a critical role in discovering new vaccine targets. This is followed by the characterization of these targets in terms of their ability to generate protective immune responses. Validation of the findings in genetically diverse populations is aided by information gained through genomics approaches. Finally, application of the findings assists in the design and completion of phase I–IV clinical trials.