Humanized influenza monoclonal antibodies and methods of use thereof
AssigneeDana-Farber Cancer Institute, Inc.
InventorWayne A. Marasco
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Abstract
The present invention provides structural determinants important for binding to the stem domain of the HA protein of influenza virus, and methods of use thereof for production of high affinity neutralizing influenza virus antibodies based upon these determinants. The present invention further provides tools for determining the efficacy of an influenza virus vaccine. The present invention further provides a molecular signature useful for determining the efficacy of an influenza virus vaccine in a subject, or for predicting prior immunologic exposure or antigen responsiveness to vaccine or influenza virus infection.
Claims20
An isolated recombinantly produced monoclonal antibody wherein said antibody has the following characteristics:
- a. a heavy chain variable region encoded by the IGHV3-30 germline gene;
- b. binds an epitope in the stem region of a hemaggluitinin (HA) protein;
- and
- c. neutralizes group 1 and group 2 influenza A viruses.
An isolated monoclonal antibody that neutralizes an influenza virus comprising
- a. a heavy chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:7;
- a CDR2 comprising the amino acid sequence of SEQ ID NO:
- 8 and a CDR3 comprising the amino acid sequence of SEQ ID NO:9;
- and
- b. a light chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NOs:10 or SEQ ID NO:14;
- a CDR2 comprising the amino acid sequence of SEQ ID NO:
- 11;
- and a CDR3 comprising the amino acid sequence of SEQ ID NO:
- 12 or SEQ ID NO:13.
An isolated monoclonal antibody wherein said antibody comprises
- a. a VH amino acid sequence of SEQ ID NO:
- 2 and a VL amino acid sequence of SEQ ID NO:
- 4 or SEQ ID NO:6;
- b. a VH amino acid sequence of SEQ ID NO:
- 2 and a VL amino acid sequence of SEQ ID NO:
- 24;
- or
- c. a VH amino acid sequence of SEQ ID NO:
- 22 and a VL amino acid sequence of SEQ ID NO:
- 4 or 6.
The antibody according to any of the preceding claims, wherein the antibody is a single chain Fv antibody, an Fab fragment, an Fab′ fragment, or an F(ab′)2 fragment.
The antibody according to any one of the preceding claims linked to a therapeutic agent.
A nucleic acid sequence comprising a nucleic acid sequence selected from SEQ ID NOs:
- 1, 3 and 5.
A nucleic acid sequence encoding a polypeptide comprising an amino acid sequences selected from SEQ ID NO:
- 2, 4 and 6.
A polypeptide comprising an amino acid sequence selected from SEQ ID NOs:
- 2, 4 and 6.
Dependencies are inferred from the claim text.