Vaccination has been among the greatest contributors to the past century’s dramatic improvements in health and life expectancy around the world. Today, nearly 30 human and many animal diseases are vaccine preventable. Despite these great advances to human and animal health, current vaccine technologies for the most part are not sufficiently effective to enable products that address many of the remaining viral, bacterial and parasitic pathogens. This is mainly due to the fact that most human and animal disease-causing microbes have evolved host-evading mechanisms inherently resistant to basic vaccine principles and technologies. Thus, a great unmet need exists for understanding and rationally designing antigens to overcome these evolved mechanisms, and to refocus the immune system to key neutralizing determinants correlating with protective immunity.
The goal of IBBR’s structure-based vaccine design approach is to control antigenicity at the atomic-level and to create immunogens capable of eliciting robust neutralizing and protective immune responses. A fundamental aspect of this paradigm involves the study of immune responses in infected individuals and vaccinated subjects to define antigenic targets of both protective and non-protective antibodies. The ability to identify and isolate antibodies from infected individuals has advanced in recent years through use of single-B-cell cloning technologies combined with next generation sequencing analyses that define the kinetics and maturation pathways of related antibody gene clusters.
Advanced structural biology tools can then be utilized to define, at the atomic level, the conformations and key sites on pathogenic proteins that render them susceptible to protective immune responses, to define those that act as immunodominant decoys for non-protective responses, and to define structural signatures of their maturation pathways. Vaccine immunogens are then engineered to re-focus immune responses to key sites of protection, to stabilize specific conformations deemed optimal for protection, to immuno-silence non-protective epitopes, and to guide maturation pathways of vaccine-elicited antibody responses in a structurally defined manner.