High affinity antibodies that neutralize
This invention provides antibodies that specifically bind and neutralize Staphylococcus enterotoxin B. In addition, nucleic acids encoding such antibodies, and cells that express such antibodies are provided. Also provided are methods for treating diseases mediated by, and for neutralizing Staphylococcus enterotoxin B.
1. An isolated vector comprising a polynucleotide encoding an antibody heavy chain comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 68, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 70.
2. The vector of claim 1 , said polynucleotide further encoding an antibody light chain comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 56, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
3. An isolated vector comprising a polynucleotide encoding an antibody light chain comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 56, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 58.
4. An isolated vector comprising a polynucleotide encoding an antibody heavy chain comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 130, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 131, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 132.
5. The vector of claim 4 , said polynucleotide further encoding an antibody light chain comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 104, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 106.
6. An isolated vector comprising a polynucleotide encoding an antibody light chain comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 104, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 106.
7. An isolated vector comprising a polynucleotide encoding an antibody heavy chain comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 92, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 94.
8. The vector of claim 7 , said polynucleotide further encoding an antibody light chain comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 80, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 81, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 82.
9. An isolated vector comprising a polynucleotide encoding an antibody light chain comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 80, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 81, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 82.
10. An isolated vector comprising a polynucleotide encoding an antibody heavy chain comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 144, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 146, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 148.
11. The vector of claim 10 , said polynucleotide further encoding an antibody light chain comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 136, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 138, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 140.
12. An isolated vector comprising a polynucleotide encoding an antibody light chain comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 136, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 138, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 140.
13. The vector of any one of claims 1 to 12 wherein said polynucleotide is a cDNA.
14. A cell that expresses a vector comprising a polynucleotide encoding an antibody, or antigen-binding fragment thereof, that binds to Staphylococcus enterotoxin B, said antibody comprising:
a. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 68, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 70, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 56, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 58;
b. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 130, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 131, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 132, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 104, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 106;
c. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 92, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 94, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 80, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 81, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 82; or
d. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 144, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 146, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 148, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 136, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 138, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 140.
15. A hybridoma cell that expresses a polynucleotide encoding an antibody, or antigen-binding fragment thereof, that binds to Staphylococcus enterotoxin B, said antibody comprising:
a. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 68, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 70, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 56, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and a light chain CDR3 comprising the amino acid sequence of SEQ IDNO: 58;
b. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 130, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 131, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 132, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 104, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 106;
c. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 92, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 94, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 80, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 81, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 82; or
d. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 144, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 146, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 148, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 136, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 138, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 140.
16. A method of making an antibody or antigen-binding fragment thereof, comprising culturing the cell of claim 14 or 15 under conditions suitable to produce the antibody or an antigen-binding fragment, and recovering the antibody or antigen-binding fragment from the cell culture.
17. An immortalized cell that expresses a polynucleotide encoding an antibody, or antigen-binding fragment thereof, that binds to Staphylococcus enterotoxin B, said antibody comprising:
a. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 68, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 69, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 70, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 56, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 57, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 58;
b. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 130, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 131, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 132, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 104, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 105, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 106;
c. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 92, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 93, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 94, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 80, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 81, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 82; or
d. a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 144, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 146, and a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 148, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 136, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 138, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 140.