CoV-2 (CoV-n) antibody neutralizing and CTL vaccines using protein scaffolds and molecular evolution

摘要

The embodiment of the invention is to innovate immunogenic CoV-2, CoV-n B cell epitopes, which are selected from the loop regions constrained by the two constraining beta strands; or between one beta strand and one alpha-helical strand; or between two alpha-helical strands of CoV-2, CoV-n proteins, and such selected loops replace the native loops of the thermostable protein scaffolds, which provide thermostable constraint of the transplanted CoV-2, CoV-n loop antigens as well as CD4 helper T cell determinants to elicit CD4 dependent neutralizing and blocking antibodies against viral entry, replication and viral clearance. The B cell loops can be cleaved and processed as CD8 T cell epitopes for eliciting cytotoxic T lymphocyte (CTL) responses against and clear viral infected cells. MHCI viral peptide epitopes in nonamers, octamers, or decamers will be used as peptide vaccines along with viral CD4 helper peptide epitopes. These CTL peptides will be also inserted into the loop or replacing the native loop of the protein scaffolds. All the above sequences can be embodied in RNA vaccines to augment protection or suppress cytokine storms. And the embodiment of the invention is to employ CTL peptides and CD4 helper peptides inserted into each respective candidate loop of the protein scaffolds as CTL vaccines. Thus, the CTL vaccines safely eliminate infectious foci and reservoir of the offending virus and mutant viral strains.