Advances in structure-based vaccine design.

TitleAdvances in structure-based vaccine design.
Publication TypeJournal Article
Year of Publication2013
AuthorsKulp DW, Schief WR
JournalCurr Opin Virol
Volume3
Issue3
Pagination322-31
Date Published06/01/2013
ISSN1879-6265
KeywordsAntibodies, Neutralizing, Antigens, Drug Discovery, Epitopes, Humans, Protein Engineering, Vaccines
Abstract

Despite the tremendous successes of current vaccines, infectious diseases still take a heavy toll on the global population, and that provides strong rationale for broadening our vaccine development repertoire. Structural vaccinology, in which protein structure information is utilized to design immunogens, has promise to provide new vaccines against traditionally difficult targets. Crystal structures of antigens containing one or more protection epitopes, especially when in complex with a protective antibody, are the launching point for immunogen design. Integrating structure and sequence information for families of broadly neutralizing antibodies (bNAbs) has recently enabled the creation of germline-targeting immunogens that bind and activate germline B-cells in order to initiate the elicitation of such antibodies. The contacts between antigen and neutralizing antibody define a structural epitope, and methods have been developed to transplant epitopes to scaffold proteins for structural stabilization, and to design minimized antigens that retain one or more key epitopes while eliminating other potentially distracting or unnecessary features. To develop vaccines that protect against antigenically variable pathogens, pioneering structure-based work demonstrated that multiple strain-specific epitopes could be engineered onto a single immunogen. We review these recent structural vaccinology efforts to engineer germline-targeting, epitope-specific, and/or broad coverage immunogens.

DOI10.1016/j.coviro.2013.05.010
Alternate JournalCurr Opin Virol
PubMed ID23806515
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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