Multi-epitope vaccine design of African swine fever virus considering T cell and B cell immunogenicity

Abstract T and B cell activation are equally important in triggering and orchestrating adaptive host responses to design multi-epitope African swine fever virus (ASFV) vaccines. However, few design methods have considered the trade-off between T and B cell immunogenicity when identifying promising ASFV epitopes. This work proposed a novel Pareto front-based ASFV screening method PFAS to identify promising epitopes for designing multi-epitope vaccines utilizing five ASFV Georgia 2007/1 sequences. To accurately predict T cell immunogenicity, four scoring methods were used to estimate the T cell activation in the four stages, including proteasomal cleavage probability, transporter associated with antigen processing transport efficiency, class I binding affinity of the major histocompatibility complex, and CD8 + cytotoxic T cell immunogenicity. PFAS ranked promising epitopes using a Pareto front method considering T and B cell immunogenicity. The coefficient of determination between the Pareto ranks of multi-epitope vaccines and survival days of swine vaccinations was R 2 = 0.95. Consequently, PFAS scored complete epitope profiles and identified 72 promising top-ranked epitopes, including 46 CD2v epitopes, two p30 epitopes, 10 p72 epitopes, and 14 pp220 epitopes. PFAS is the first method of using the Pareto front approach to identify promising epitopes that considers the objectives of maximizing both T and B cell immunogenicity. The top-ranked promising epitopes can be cost-effectively validated in vitro . The Pareto front approach can be adaptively applied to various epitope predictors for bacterial, viral and cancer vaccine developments. The MATLAB code of the Pareto front method was available at https://github.com/NYCU-ICLAB/PFAS.