Abstract
The use of protein X-ray crystallography for structure-based design of small-molecule drugs is well-documented and includes several notable success stories. However, it is less well-known that structural biology has emerged as a major tool for the design of novel vaccine antigens. Here, we review the important contributions that protein crystallography has made so far to vaccine research and development. We discuss several examples of the crystallographic characterization of vaccine antigen structures, alone or in complexes with ligands or receptors. We cover the critical role of high-resolution epitope mapping by reviewing structures of complexes between antigens and their cognate neutralizing, or protective, antibody fragments. Most importantly, we provide recent examples where structural insights obtained via protein crystallography have been used to design novel optimized vaccine antigens. This review aims to illustrate the value of protein crystallography in the emerging discipline of structural vaccinology and its impact on the rational design of vaccines.
Highlights
Vaccination first began in the 18th Century when Edward Jenner protected humans from smallpox by administering material from humans infected with cowpox
This review aims to provide a concise survey of several recent advances in vaccine research and development that have been driven by insights obtained from protein crystallography
We have reviewed how protein crystallography can play a key role in vaccine research and development processes
Summary
Vaccination first began in the 18th Century when Edward Jenner protected humans from smallpox by administering material from humans infected with cowpox. Additional major vaccine developments in the 20th Century provided protection against diphtheria, tetanus, pertussis, polio, several types of meningococcus and pneumococcus, haemophilus influenzae B, hepatitis and influenza. These vaccines have eliminated most of the life-threatening childhood diseases that previously caused millions of deaths and severe morbidity, rendering vaccination one of the most effective medical interventions in history [1,2]. Approach, which overcame challenges that had not been resolved via conventional vaccinology [4] It was the whole-genome sequencing of Neisseria meningitidis serogroup B that enabled the development of reverse vaccinology for the identification of recombinant antigens for a protein-based vaccine against serogroup B meningococcus [5,6]. We conclude with an outlook of how we expect the field to evolve in the near future
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