Principles and practical applications of structure-based vaccine design

ElsevierVolume 77, August 2022, 102209Current Opinion in ImmunologyHighlights•

Summary of the basic principles of structure-based vaccine design.

Review of recent advances (the years 2019–2021) in structure-based vaccine design.

Preview of outstanding challenges facing the vaccine-design field.

Viral proteins fold into a variety of structures as they perform their functions. Structure-based vaccine design aims to exploit knowledge of an antigen’s architecture to stabilize it in a vulnerable conformation. We summarize the general principles of structure-based vaccine design, with a focus on the major types of sequence modifications: proline, disulfide, cavity-filling, electrostatic and hydrogen-bond substitution, as well as domain deletion. We then review recent applications of these principles to vaccine-design efforts across five viral families: Coronaviridae, Orthomyxoviridae, Paramyxoviridae, Pneumoviridae, and Filoviridae. Outstanding challenges include continued application of proven design principles to pathogens of interest, as well as development of new strategies for those pathogens that resist traditional techniques.

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