Toward rational vaccine engineering

Technological revolutions in several fields have pushed the boundaries of vaccine design and provided new avenues for vaccine development. Next-generation vaccine platforms have shown promise in targeting challenging antigens, for which traditional approaches have been ineffective. With advances in protein engineering, structural biology, computational biology and immunology, the structural vaccinology approach, which uses protein structure information to develop immunogens, holds promise for future vaccine design. In this review, we highlight various vaccine development strategies, along with their advantages and limitations. We discuss the rational vaccine design approach, which focuses on structure-based vaccine design. Finally, we discuss antigen engineering using the epitope-scaffold approach, gaps in structural vaccinology, and remaining challenges in vaccine design.