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AssigneeSwey-Shen Chen
InventorSwey-Shen Chen
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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.
We claim the B cell antigenic epitopes of the CoV-2 surface spike protein (S), ORF1a, ORF-1ab, leader protein, nsp-2, nsp-3, nsp-4, 3C-like proteinase, nsp-5, nsp-6, nsp-7, nsp-8, nsp-9, nsp-10, RNA-dependent RNA polymerase, helicase, 3→5′ exonuclease, endoRNAse, 2-O′ ribose methyltransferase, ORF-3a, E, M, ORF-6, N, ORF-7a, ORF-7b, ORF-8, nucleocapsid, and CoV-n thereof that are conformationally constrained by, and replacing the native loop constrained by the beta strands of the scaffold proteins such as lipocalin, GFP, fibronectin, and CDR regions delineated by the beta strands of the immunoglobulin light and heavy chains.
We claim the CTL antigenic epitopes of the CoV-2 surface spike protein (S), ORF1a, ORF-1ab, leader protein, nsp-2, nsp-3, nsp-4, 3C-like proteinase, nsp-5, nsp-6, nsp-7, nsp-8, nsp-9, nsp-10, RNA-dependent RNA polymerase, helicase, 3→5′ exonuclease, endoRNAse, 2-O′ ribose methyltransferase, ORF-3a, E, M, ORF-6, N, ORF-7a, ORF-7b, ORF-8, nucleocapsid, and CoV-n variants thereof, wherein these CTL epitopes are nonamer, and can be octameric (−1) or decameric (+) peptides;
We claim truncated polypeptides of CoV-2 surface spike protein (S), ORF1a, ORF-1ab, leader protein, nsp-2, nsp-3, nsp-4, 3C-like proteinase, nsp-5, nsp-6, nsp-7, nsp-8, nsp-9, nsp-10, RNA-dependent RNA polymerase, helicase, 3→5′ exonuclease, endoRNAse, 2-O′ ribose methyltransferase, ORF-3a, E, M, ORF-6, N, ORF-7a, ORF-7b, ORF-8, nucleocapsid, and CoV-n variants thereof, that are recombinantly fused to the N-terminus or C-terminus of the protein scaffolds such as lipocalin, GFP, fibronectin, and CDR regions delineated by the beta strands of the immunoglobulin light and heavy chains.
Dependencies are inferred from the claim text.