Computational Approaches and Challenges to Developing Universal Influenza Vaccines.

The traditional design of effective vaccines for rapidly-evolving pathogens, such as influenza A virus, has failed to provide broad spectrum and long-lasting protection. With low cost whole genome sequencing technology and powerful computing capabilities, novel computational approaches have demonstrated the potential to facilitate the design of a universal influenza vaccine. However, few studies have integrated computational optimization in the design and discovery of new vaccines. Understanding the potential of computational vaccine design is necessary before these approaches can be implemented on a broad scale. This review summarizes some promising computational approaches under current development, including computationally optimized broadly reactive antigens with consensus sequences, phylogenetic model-based ancestral sequence reconstruction, and immunomics to compute conserved cross-reactive T-cell epitopes. Interactions between virus-host-environment determine the evolvability of the influenza population. We propose that with the development of novel technologies that allow the integration of data sources such as protein structural modeling, host antibody repertoire analysis and advanced phylodynamic modeling, computational approaches will be crucial for the development of a long-lasting universal influenza vaccine. Taken together, computational approaches are powerful and promising tools for the development of a universal influenza vaccine with durable and broad protection.