CoV-2 (CoV-n) antibody neutralizing and CTL vaccines using protein scaffolds and molecular evolution
OwnerSwey-Shen Cheninventor
Life of this patent
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Abstract
The embodiment of the invention is to conformationally constrain neutralizing B cell epitopes of CoV-2, CoV-n B cell epitopes of the open reading frame proteins, including the membrane S protein, constrained by protein scaffolds, including camelid VHH nanobody in order to elicit neutralizing and blocking antibodies against viral infection. B cell epitopes are molecularly evolved by ribosome display to preempt emerging viral B cell epitopes. Moreover, CTL epitopes are designed from the open reading frame protein for eliciting cell mediated viral protection. Furthermore, mRNA vaccines are prepared for eliciting protective immunity and prevent cytokine storms.
Claims14
A composition comprising recombinant B cell antigenic epitopes chemically modified from the CoV-2 surface spike protein (S) (SEQ ID NO:
- 1243), comprising and not limited to NTD (SEQ ID NO:
- 1 to SEQ ID NO:
- 10, SEQ ID NO:
- 1244), RBD/RBE (SEQ ID NO:
- 11 to SEQ ID NO:17, SEQ ID NO:
- 37 to SEQ ID NO:
- 42, SEQ ID NO:
- 1215 to SEQ ID NO:
- 1220) and S1-S2 furin junction (SEQ ID NO:
- 18 to SEQ ID NO:
- 36, SEQ ID NO:
- 1221 to SEQ ID NO:
- 1223, SEQ ID NO:
- 1252 to SEQ ID NO:
- 1254), wherein said chemically modified recombinant antigenic B cell epitopes are in protein scaffolds comprising but not limited to CDRs of camelid VHH (SEQ ID NO:
- 1255, SEQ ID NO:
- 1260), lipocalin (SEQ ID NO:
- 1258, SEQ ID NO:1263), GFP (SEQ ID NO:
- 1257, SEQ ID NO:
- 1262), fibronectin (SEQ ID NO:
- 1281, SEQ ID NO:
- 1282), ankyrin repeat (SEQ ID NO:
- 1256, SEQ ID NO:
- 1261), VH3 (SEQ ID NO:
- 1259, SEQ ID NO:
- 1264), and wherein said chemically modified recombinant B cell antigenic epitopes of CoV-2 S protein in said protein scaffolds as chemically modified recombinant vaccine products, whereby said chemically modified combinatory recombinant vaccine products are employed to vaccinate human population to prevent CoV-2 infection.
A composition comprising chemically modified recombinant nonameric peptides (+1/−1) into recombinant CDR1, CDR2 and CDR3 of VHH (SEQ ID NO:
- 1255, SEQ ID NO:
- 1260), chemically derived from CoV-2 open reading frame proteins, comprising spike protein (SEQ ID:
- 60 to SEQ ID:
- 235);
- NC protein (SEQ ID:
- 236 to SEQ ID:
- 280);
- ORF1a (SEQ ID:
- 314 to SEQ ID:
- 395), rdrp protein (SEQ ID:
- 396 to SEQ ID:
- 571);
- helicase protein (SEQ ID:
- 572 to SEQ ID:
- 699);
- Exonuclease 5>3 (SEQ ID:
- 700 to SEQ ID:
- 803);
- endoRNAse (SEQ ID:
- 804 to SEQ ID:
- 882);
- methyltransferase protein (SEQ ID:
- 883 to SEQ ID:
- 953);
- membrane protein (SEQ ID:
- 954 to SEQ ID:
- 1014);
- envelope protein (SEQ ID:
- 1015 to SEQ ID:
- 1044);
- ORF-3a protein (SEQ ID:
- 1045 to SEQ ID:
- 1112);
- ORF-6 protein (SEQ ID:
- 1113 to SEQ ID:
- 1125);
- ORF-7 protein (SEQ ID:
- 1126 to SEQ ID:
- 1135);
- ORF-8 protein (SEQ ID:
- 1136 to SEQ ID:
- 1174), wherein said chemically modified recombinant nonamers of said CoV-2 open reading frame proteins are used ad as recombinant nonameric VHH (SEQ ID NO:
- 1255, SEQ ID NO:
- 1260) recombinant vaccine products, whereby said chemically modified recombinant vaccines elicit cytotoxic T lymphocytes, preventing CoV-2 infection in vaccinated population.
A composition comprising mRNA vaccines, wherein the chemically modified CoV-2 open reading frame genes (SEQ ID NO:
- 1228 to SEQ ID NO:
- 1251) and chemically modified nonamer (+1/−1) to spike protein (SEQ ID:
- 60 to SEQ ID:
- 235);
- NC protein (SEQ ID:
- 236 to SEQ ID:
- 280);
- ORF1a (SEQ ID:
- 314 to SEQ ID:
- 395), rdrp protein (SEQ ID:
- 396 to SEQ ID:
- 571);
- helicase protein (SEQ ID:
- 572 to SEQ ID:
- 699);
- Exonuclease 5>3 (SEQ ID:
- 700 to SEQ ID:
- 803);
- endoRNAse (SEQ ID:
- 804 to SEQ ID:
- 882);
- methyltransferase protein (SEQ ID:
- 883 to SEQ ID:
- 953);
- membrane protein (SEQ ID:
- 954 to SEQ ID:
- 1014);
- envelope protein (SEQ ID:
- 1015 to SEQ ID:
- 1044);
- ORF-3a protein (SEQ ID:
- 1045 to SEQ ID:
- 1112);
- ORF-6 protein (SEQ ID:
- 1113 to SEQ ID:
- 1125);
- ORF-7 protein (SEQ ID:
- 1126 to SEQ ID:
- 1135);
- ORF-8 protein (SEQ ID:
- 1136 to SEQ ID:
- 1174), are chemically modified to motifs of mRNA vaccines (SEQ ID NO:
- 1175 to SEQ ID NO:
- 1180), and wherein said mRNA vaccines are employed as CoV-2 vaccines, whereby immune protection and suppression for cytokine storms are ensured.
Dependencies are inferred from the claim text.