Norovirus antibodies
Inventors
HANSMAN, Grant • KOROMYSLOVA, Anna
Assignees
Publication Number
US-11555063-B2
Publication Date
2023-01-17
Expiration Date
2038-09-19
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Abstract
The present invention relates to a binding polypeptide specifically binding to an epitope comprised in an amino acid sequence corresponding to amino acids 250 to 300 of the norovirus genotype II.10 capsid polypeptide, and to a polynucleotide encoding the same. The present invention further relates to a composition comprising the binding polypeptide according to the present invention and a carrier, and to the binding polypeptide or the composition comprising the same use in diagnosis and/or for use in medicine. Further more, the present invention relates to kits, devices, vaccines, methods, and uses related to the binding polypeptide of the present invention.
Core Innovation
The invention relates to binding polypeptides that specifically bind to an epitope within the amino acid sequence corresponding to residues 250 to 300 of the norovirus genotype II.10 capsid polypeptide. This binding polypeptide, preferably an antibody such as a single-domain antibody (VHH), specifically recognizes an epitope that includes the motif D-x-E-L-x-G-x-T within this region. The polypeptides exhibit high affinity and specificity for the norovirus capsid, enabling their use in diagnostics, medicine, disinfectants, and vaccine development.
The problem addressed by the invention is the difficulty in preventing norovirus infection and the lack of broadly reactive antibodies capable of detecting multiple norovirus strains. Existing antibodies bind limited epitopes and are hindered by the structural occlusion of binding sites in the viral capsid. Furthermore, noroviruses cannot be easily cultured, impeding vaccine and antiviral development. The invention aims to provide improved antibodies that overcome these challenges by targeting a conserved and immunodominant epitope, allowing for broad detection and potential neutralization of diverse norovirus genotypes.
Claims Coverage
The patent contains several independent claims presenting inventive features related to a binding polypeptide, its specific binding epitopes, and compositions containing it.
Binding polypeptide specificity and structure
A binding polypeptide specifically binding to an epitope comprised in amino acids 250 to 300 of norovirus genotype II.10 capsid polypeptide, wherein the binding polypeptide is a single-domain antibody (VHH) comprising the complementarity determining regions (CDRs) of SEQ ID NOs:13, 15, and 17.
Epitope localization within the capsid protein
The epitope recognized by the binding polypeptide is comprised within amino acids 260 to 280 of the norovirus genotype II.10 capsid polypeptide, including motifs such as a-x-a-h-x-h-x-o.
Dual epitope binding capability
The binding polypeptide further specifically binds to a second epitope comprised in amino acids 450 to 490 of the norovirus genotype II.10 capsid polypeptide, where this second epitope comprises motifs N or Q-D or E and can include the motif Y-Q-E-S-x-P-(x)12-P.
Composition incorporating the binding polypeptide
A composition comprising the binding polypeptide and a carrier, optionally including Nano-85 that specifically binds a distinct epitope W-V-N-x-F-Y-x on norovirus capsid polypeptides, forming a pharmaceutical composition.
Application method
A method comprising contacting a subject and/or an object suspected to comprise a norovirus particle with the binding polypeptide to diagnose, treat, prevent, or inactivate norovirus infection.
The claims cover the specific binding polypeptide targeting conserved epitopes of the norovirus capsid protein, compositions containing these polypeptides including pharmaceutical formulations, and methods of use directed to diagnosis, treatment, prevention, and inactivation of norovirus.
Stated Advantages
The binding polypeptide broadly recognizes members of the norovirus genus allowing for broad norovirus detection in diagnostic tests.
The antibody can potentially inhibit norovirus infection without prior knowledge of genotype, thus acting broadly.
The binding polypeptide can inactivate norovirus particles by binding to specific epitopes, preventing viral spread.
It is useful for sanitization and disinfection purposes due to its capacity to inactivate norovirus.
Nanobodies are easy and cost-effective to produce, enabling low-cost detection kits and permitting high-density application on surfaces, which improves assay sensitivity.
The binding polypeptide synergizes with previously described antibodies (e.g., Nano-85) to disassemble norovirus capsids more effectively.
Documented Applications
Use in diagnostic methods and kits for detecting norovirus infection by binding specifically to conserved capsid epitopes.
Use in medicine for treating or preventing norovirus infections in subjects by administration of the binding polypeptide or compositions thereof.
Use in compositions and methods for inactivating norovirus particles, including in disinfectants for surfaces or body surfaces.
Development of vaccines comprising peptides including the identified conserved epitope within amino acids 250 to 300 of the norovirus genotype II.10 capsid polypeptide.
Kits and devices for diagnosing, preventing, or treating norovirus infection comprising the binding polypeptide and optionally other components like protease, RNase, detergents, and additional antibodies.
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