A novel approach to designing viral precision vaccines applied to SARS-CoV-2

Abstract Efficient precision vaccines against several highly pathogenic zoonotic viruses are currently lacking. Here, we describe a new approach to developing viral precision vaccines based on specific antigen selection through its application to the design of a SARS-CoV-2 cross-variant vaccine. This approach targets viral structural regions involved in infectivity to identify conserved immunogenic epitopes and select those eliciting specific immune responses in infected people. An important step of this approach consists of engineering vaccinating antigens that carry the selected epitopes and mimic their 3D native structure. In our study, the epitopes selected from SARS-CoV-2 revealed an antibody response significantly associated with mild and asymptomatic COVID-19, which strongly suggests protective immunity. Engineered antigens containing the SARS-CoV-2 selected epitopes generated a robust antibody response in mice. Limitations include the need for animal challenge with live virus. Taken together, our results show the potential of this approach for designing precision viral vaccines.