Monoclonal antibodies against influenza virus generated by cyclical administration and uses thereof
AssigneeIcahn School of Medicine at Mount Sinai
InventorsAdolfo Garcia-Sastre, Peter Palese, Taia T. Wang
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Abstract
Provided herein are methods of producing neutralizing monoclonal antibodies, by cyclical immunization, that cross-react with strains of Influenza virus of the same subtype or different subtypes. Also provided herein are compositions comprising such antibodies and methods of using such antibodies to diagnose, prevent or treat Influenza virus disease.
Claims36
A hybridoma
- (a) designated 7A7 deposited under provisions of the Budapest Treaty with the American Type Culture Collection (ATCC, 10801 University Blvd., Manassas, Va. 20110-2209) on May 22, 2009 (ATCC Accession No. PTA-10058),
- (b) designated 12D1 deposited under provisions of the Budapest Treaty with the American Type Culture Collection (ATCC, 10801 University Blvd., Manassas, Va. 20110-2209) on May 22, 2009 (ATCC Accession No. PTA-10059),
- (c) designated 39A4 deposited under provisions of the Budapest Treaty with the American Type Culture Collection (ATCC, 10801 University Blvd., Manassas, Va. 20110-2209) on May 22, 2009 (ATCC Accession No. PTA-10060), or
- (d) designated 66A6 deposited under provisions of the Budapest Treaty with the American Type Culture Collection (ATCC, 10801 University Blvd., Manassas, Va. 20110-2209) on May 26, 2010 (ATCC Accession No. PTA-11046).
An isolated antibody that binds to SEQ ID NO:1, SEQ ID NO:124, or SEQ ID NO:125, and neutralizes two or more strains of an Influenza A virus HA subtype.
An isolated antibody that binds to Influenza A virus of the H3 subtype, the antibody comprising (a) the variable heavy (VH) domain of the antibody 7A7, 12D1, 39A4, or 66A6;
- (b) the variable light (VL) domain of the antibody 7A7, 12D1, 39A4, or 66A6;
- (c) the VH domain of the antibody 7A7, 12D1, 39A4, or 66A6and the VL domain of the antibody 7A7, 12D1, 39A4, or 66A6;
- (d) the VH complementarity determining regions (CDRs) of the antibody 7A7, 12D1, 39A4, or 66A6;
- (e) the VL CDRs of the antibody 7A7, 12D1, 39A4, or 66A6;
- or (f) the VH CDRs of the antibody 7A7, 12D1, 39A4, or 66A6and the VL CDRs of the antibody 7A7, 12D1, 39A4, or 66A6.
An isolated nucleic acid encoding an antibody that binds to Influenza A virus of the H3 subtype, wherein the antibody comprises (a) the amino acid sequence of the VH domain of the antibody 7A7, 12D1, 39A4, or 66A6;
- (b) the amino acid sequence of the VL domain of the antibody 7A7, 12D1, 39A4, or 66A6;
- (c) the amino acid sequence of the VH domain of the antibody 7A7, 12D1, 39A4, or 66A6and the VL domain of the antibody 7A7, 12D1, 39A4, or 66A6;
- (d) the amino acid sequence of the VH CDRs of the antibody 7A7, 12D1, 39A4, or 66A6;
- (e) the amino acid sequence of the VL CDRs of the antibody 7A7, 12D1, 39A4, or 66A6;
- or (f) the VH CDRs of the antibody 7A7, 12D1, 39A4, or 66A6and the VL CDRs of the antibody 7A7, 12D1, 39A4, or 66A6.
An isolated antibody that binds to Influenza A virus of the H3 subtype, the antibody comprising
- (a) a heavy chain variable region comprising a complementarity determining region (CDR)1 having the amino acid sequence of SEQ ID NO:38, a CDR2 having the amino acid sequence of SEQ ID NO:39, and a CDR3 having the amino acid sequence of SEQ ID NO:40;
- and a light chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO:46, a CDR2 having the amino acid sequence of SEQ ID NO:47, and a CDR3 having the amino acid sequence of SEQ ID NO:48;
- (b) a heavy chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO:70, a CDR2 having the amino acid sequence of SEQ ID NO:71, and a CDR3 having the amino acid sequence of SEQ ID NO:72;
- and a light chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO:78, a CDR2 having the amino acid sequence of SEQ ID NO:79, and a CDR3 having the amino acid sequence of SEQ ID NO:80;
- (c) a heavy chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO:92, a CDR2 having the amino acid sequence of SEQ ID NO:93, and a CDR3 having the amino acid sequence of SEQ ID NO:94;
- and a light chain variable region comprising a CDR1 having the amino acid sequence of SEQ ID NO:100, a CDR2 having the amino acid sequence of SEQ ID NO:
- 101, and a CDR3 having the amino acid sequence of SEQ ID NO:102;
- or
- (d) a heavy chain variable region comprising a CDR1 of the antibody 39A4, a CDR2 of the antibody 39A4, and a CDR3 of the antibody 39A4;
- and a light chain variable region comprising a CDR1 of the antibody 39A4, a CDR2 of the antibody 39A4, and a CDR3 of the antibody 39A4.
Dependencies are inferred from the claim text.