Combinations of anti-
The present disclosure is directed to anti- Staphylococcus aureus antibody combinations including combinations of antibodies that bind to S. aureus alpha toxin (AT) protein, clumping factor A protein (ClfA), and/or at least one leukotoxin protein. Methods of treating and preventing infections comprising administering the antibody combinations are also provided herein.
1. A method of treating a Staphylococcus aureus ( S. aureus ) infection in a subject comprising administering to the subject (a) an antibody or antigen-binding fragment thereof that binds to S. aureus alpha toxin (AT) and comprises a variable heavy chain (VH) comprising the amino acid sequence of SEQ ID NO:19 and a variable light chain (VL) comprising the amino acid sequence of SEQ ID NO:33, (b) an antibody or antigen-binding fragment thereof that binds to S. aureus clumping factor A (ClfA) and comprises a VH comprising the amino acid sequence of SEQ ID NO:20 and a VL comprising the amino acid sequence of SEQ ID NO:34, and (c) an antibody or antigen-binding fragment thereof that binds to at least one S. aureus leukotoxin and comprises a VH comprising the amino acid sequence of SEQ ID NO:32 and comprises a VL comprising the amino acid sequence of SEQ ID NO:46.
2. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof that binds to S. aureus ClfA comprises a heavy chain constant domain comprising the amino acid sequence of CSYHLC (SEQ ID NO:55).
3. The method of claim 2 , wherein said heavy chain constant domain comprises the amino acid sequence of MHEACSYHLCQKSLSLS (SEQ ID NO:56).
4. The method of claim 1 , wherein the S. aureus infection is sepsis, bacteremia, pneumonia, ICU pneumonia, a skin or soft tissue infection (SSTI), a diabetic infection of the lower limbs, a diabetic foot ulcer (DFU), a bone infection, a joint infection, a device infection, a wound infection, a surgical site infection, and/or osteomyelitis.
5. The method of claim 1 , wherein the treating an S. aureus infection comprises inhibiting S. aureus agglutination, toxin neutralization, inducing opsonophagocytosis, inhibiting S. aureus fibrinogen binding, inhibiting thromboembolic lesion formation, inhibiting S. aureus -associated sepsis, or any combination of the foregoing.
6. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof that binds to S. aureus AT, the antibody or antigen-binding fragment thereof that binds to S. aureus ClfA, and/or the antibody or antigen-binding fragment thereof that binds to at least one S. aureus leukotoxin are administered in the same pharmaceutical composition.
7. The method of claim 1 , wherein the S. aureus is antibiotic-resistant S. aureus.
8. The method of claim 1 , wherein (a) the antibody that binds to S. aureus AT is an IgG antibody, (b) the antibody that binds to S. aureus ClfA is an IgG antibody, and (c) the antibody that binds to at least one S. aureus leukotoxin is an IgG antibody.
9. The method of claim 8 , wherein the S. aureus infection is sepsis, bacteremia, pneumonia, ICU pneumonia, a skin or soft tissue infection (SSTI), a diabetic infection of the lower limbs, a diabetic foot ulcer (DFU), a bone infection, a joint infection, a device infection, a wound infection, a surgical site infection, and/or osteomyelitis.
10. The method of claim 8 , wherein the S. aureus is antibiotic-resistant S. aureus.
11. The method of claim 1 , wherein (a) the antibody that binds to S. aureus AT is an IgG1 antibody, (b) the antibody that binds to S. aureus ClfA is an IgG1 antibody, and (c) the antibody that binds to at least one S. aureus leukotoxin is an IgG1 antibody.
12. The method of claim 11 , wherein the S. aureus infection is sepsis, bacteremia, pneumonia, ICU pneumonia, a skin or soft tissue infection (SSTI), a diabetic infection of the lower limbs, a diabetic foot ulcer (DFU), a bone infection, a joint infection, a device infection, a wound infection, a surgical site infection, and/or osteomyelitis.
13. The method of claim 11 , wherein the S. aureus is antibiotic-resistant S. aureus.
14. The method of claim 1 , wherein (a) the antibody that binds to S. aureus AT comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:47 and a light chain comprising the amino acid sequence of SEQ ID NO:52, (b) the antibody that binds to S. aureus ClfA comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:49 and a light chain comprising the amino acid sequence of SEQ ID NO:53, and (c) the antibody that binds to at least one S. aureus leukotoxin comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:50 and a light chain comprising the amino acid sequence of SEQ ID NO:54.
15. The method of claim 14 , wherein the S. aureus infection is sepsis, bacteremia, pneumonia, ICU pneumonia, a skin or soft tissue infection (SSTI), a diabetic infection of the lower limbs, a diabetic foot ulcer (DFU), a bone infection, a joint infection, a device infection, a wound infection, a surgical site infection, and/or osteomyelitis.
16. The method of claim 15 , wherein the S. aureus is antibiotic-resistant S. aureus.
17. The method of claim 14 , wherein the S. aureus is antibiotic-resistant S. aureus.
18. The method of claim 14 , wherein the S. aureus infection is a diabetic foot ulcer (DFU).
19. The method of claim 14 , wherein the S. aureus infection is a diabetic infection of the lower limbs.
20. The method of claim 1 , wherein (a) the antibody that binds to S. aureus AT comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:48 and a light chain comprising the amino acid sequence of SEQ ID NO:52, (b) the antibody that binds to S. aureus ClfA comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:70 and a light chain comprising the amino acid sequence of SEQ ID NO:53, and (c) the antibody that binds to at least one S. aureus leukotoxin comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:51 and a light chain comprising the amino acid sequence of SEQ ID NO:54.
21. The method of claim 1 , wherein the S. aureus infection is a diabetic foot ulcer (DFU).
22. The method of claim 1 , wherein the S. aureus infection is a diabetic infection of the lower limbs.