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Patent US10676511
Issued 2020-06-09
Coronaviruses Epitope-based Vaccines
Provided are polypeptides derived from the coronaviruses (CoVs) Spike protein (S) characterized by high affinity and specificity the S receptor and its neutralizing antibodies. Further provided are compositions and vaccines, and vaccine-based therapies targeting CoVs, and SARS and MERS viruses in particular.
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- 1. A polypeptide comprising an amino acid sequence of at least one reconstituted Receptor Binding Motif (RBM) of a Spike protein of a Coronavirus (CoV) or of any fragment thereof, wherein said reconstituted RBM comprises at least one non-native linker and at least two fragments of the native RBM, said native RBM is a 30 to 200 amino acid sequence comprised within the Receptor Binding Domain (RBD) of said Spike protein forming a binding interface that interacts with the viral receptor, wherein said native RBM forms an extended 30 to 100 or more amino acid excursion juxtaposed along the edge of the core of the RBD and tacked to said core via a loop, and wherein at least one of said linker/s replaces or is added to at least one of: said loop, any part or amino acid residue/s thereof and any RBM fragment or amino acid residue/s thereof.
- 15. A method for preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of an infection or an infectious clinical condition caused by coronavirus, or of inducing an immune response against a coronavirus, in a subject in need thereof, the method comprising the step of administrating to said subject an effective amount of at least one polypeptide comprising an amino acid sequence of at least one reconstituted RBM of CoV Spike protein or of any fragment thereof, any derivative, enantiomer, fusion protein, conjugate or polyvalent dendrimer thereof or of any composition or vaccine comprising the same, wherein said reconstituted RBM comprises at least one linker and at least two fragments of the native RBM, said native RBM is a 30 to 200 amino acid sequence comprised within the RBD of said Spike protein forming a binding interface that interacts with the viral receptor.
- 17. A method for the preparation of a functional reconstituted RBM of Spike protein of a CoV, said method comprises the step of:
a) providing a conformer library of RBMs of said Spike protein of a CoV, comprising plurality of bacteriophages, each expressing a reconstituted RBM comprising an amino acid sequence of at least two fragments of an RBM of a viral Spike protein of a CoV and at least one exogenous combinatorial linker; b) screening said library with a binding molecule; and c) identifying and producing reconstituted RBM peptides which bind at least one of said binding molecules.
