title: Protein Crystallography in Vaccine Research and Development.
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.
authors.affiliation: Protein Biochemistry Department, Novartis Vaccines & Diagnostics s.r.l. (a GSK Company), Via Fiorentina 1, 53100 Siena, Italy. enrico.x.malito@gsk.com.
authors.forename: Enrico
authors.initials: E
authors.lastname: Malito
authors.affiliation: Protein Biochemistry Department, GSK Vaccines, Cambridge, MA 02139, USA. andrea.x.carfi@gsk.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carfi
authors.affiliation: Protein Biochemistry Department, Novartis Vaccines & Diagnostics s.r.l. (a GSK Company), Via Fiorentina 1, 53100 Siena, Italy. matthew.j.bottomley@gsk.com.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bottomley
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry* / Q000276:immunology; D001666:Binding Sites, Antibody; D003461:Crystallography; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D014614:Vaccines, Synthetic / Q000737:chemistry* / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D000956:Antigens, Viral; D000939:Epitopes; D014614:Vaccines, Synthetic
keywords: Staphylococcus aureus; crystallization; human immunodeficiency virus (HIV); meningitis; paratope; protein engineering; respiratory syncytial virus (RSV)