Application of germline antibody features to vaccine development, antibody discovery, antibody optimization and...

Although the efficacy and commercial success of vaccines and therapeutic antibodies have been tremendous, designing and discovering new drug candidates remains a labor-, time- and cost-intensive endeavor with high risks. The main challenges of vaccine development are inducing a strong immune response in broad populations and providing effective prevention against a group of highly variable pathogens. Meanwhile, antibody discovery faces several great obstacles, especially the blindness in antibody screening and the unpredictability of the developability and druggability of antibody drugs. These challenges are largely due to poorly understanding of germline antibodies and the antibody responses to pathogen invasions. Thanks to the recent developments in high-throughput sequencing and structural biology, we have gained insight into the germline immunoglobulin (Ig) genes and germline antibodies and then the germline antibody features associated with antigens and disease manifestation. In this review, we firstly outline the broad associations between germline antibodies and antigens. Moreover, we comprehensively review the recent applications of antigen-specific germline antibody features, physicochemical properties-associated germline antibody features, and disease manifestation-associated germline antibody features on vaccine development, antibody discovery, antibody optimization, and disease diagnosis. Lastly, we discuss the bottlenecks and perspectives of current and potential applications of germline antibody features in the biotechnology field.