Human broadly neutralizing monoclonal antibodies associated with hepatitisc virus clearance
AssigneeThe Johns Hopkins University
InventorsJustin R. Bailey, Clinton O. Ogega
Life of this patent
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Abstract
Broadly-neutralizing antibodies (bNAbs) associated with clearance of human hepatitis C virus (HCV) infection are provided. The bNAbs were generated against a novel mixture of full-length E2 ectodomain proteins to isolate 10,680 E2-reactive B cells from acute infection through multiple spontaneous viral clearance events.
Claims24
A method of producing neutralizing antibodies to hepatitis virus comprising:
- isolating antigenically diverse proteins from the hepatitis virus,
- incubating peripheral blood mononuclear cells (PBMCs) with a mixture of the isolated antigenic diverse proteins,
- sorting the PBMCs to obtain antigen reactive class-switched memory B cells and non antigen reactive class-switched memory B cells,
- seeding the antigen reactive class-switched memory B cell cells in limiting dilutions in cell culture wells wherein each cell culture well comprises at least one antigen reactive class-switched memory B cell,
- stimulating the class-switched memory B cell cultures with one or more cytokines and antigen,
- isolating supernatants from the antigen reactive class-switched memory B cell cultures, and,
- producing neutralizing antibodies to hepatitis virus.
The method of claim 4, wherein the antigenically diverse proteins isolated from the HCV comprise E2 ectodomain proteins.
14-18. (canceled)
An isolated nucleic acid comprising:
- (i) a variable heavy chain having at least a 90% sequence identity to SEQ ID NOs:
- 1-57 or 58;
- or (ii) a variable kappa light (Vκ) chain having at least a 90% sequence identity to SEQ ID NOs:
- 59-107 or 108;
- or (iii) a variable lambda light (Vλ) chain having at least a 90% sequence identity to SEQ ID NOs:
- 109-122 or 123, or combinations thereof.
21-23. (canceled)
26-28. (canceled)
A method of preventing or treating a hepatitis C virus (HCV) infection comprising:
- administering to a subject a therapeutically effective amount of an HCV neutralizing antibody,
- thereby, treating the subject.
32-42. (canceled)
Dependencies are inferred from the claim text.