Structure-Based Design for High-Hanging Vaccine Fruits

Although vaccines have proven life saving against a myriad of infectious diseases, various pathogens have remained refractory to prophylaxis of their host by active immunization. New insights in the three dimensional (3D) structure, domain organization and dynamics of viral and bacterial surface proteins can guide the design of effective vaccines in several ways. In this review we highlight recent developments in structure-based vaccine design that are aimed at stabilization of native conformations and focusing immune response to conserved epitopes. Detailed 3D structures of pathogen surface proteins provide knowledge on how to minimize complex antigens or how to redesign the surface of an immunogen in order to induce only relevant neutralizing antibodies against a broad range of serotypes. Structure - based vaccines with reduced complexity and broad efficacy could greatly enhance the number of people that might benefit from the therapies that are developed.