Methods of treating
The present invention provides for methods of preventing and/or treating S. aureus -associated bacteremia and sepsis, and methods for preventing and/or treating S. aureus -associated pneumonia in immunocompromised patients using anti- S. aureus alpha-toxin (anti-AT) antibodies. Also provided are methods of reducing S. aureus bacterial load in the bloodstream or heart of a mammalian subject comprising administering to the subject an effective amount of an isolated anti- S. aureus alpha toxin (anti-AT) antibody or antigen-binding fragment thereof. Methods of reducing S. aureus bacterial agglutination and/or thromboembolic lesion formation in a mammalian subject comprising administering to the subject an effective amount of an isolated anti- S. aureus alpha toxin (anti-AT) antibody or antigen-binding fragment thereof, are also provided. Also provided are methods of preventing or reducing the severity of S. aureus associated pneumonia in an immunocompromised mammalian subject.
1. A method of preventing or reducing the severity of Staphylococcus aureus -associated ( S. aureus -associated) pneumonia in an immunocompromised mammalian subject, comprising administering to said subject an effective amount of an isolated anti- S. aureus alpha toxin (anti-AT) antibody or antigen-binding fragment thereof, wherein the isolated antibody or antigen-binding fragment thereof immunospecifically binds to a S. aureus alpha toxin polypeptide and includes:
(a) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 69;
(b) a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 70;
(c) a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 71;
(d) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 1;
(e) a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 2; and
(f) a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 68.
2. The method of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable domain of SEQ ID NO: 57.
3. The method of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof comprises a light chain variable domain of SEQ ID NO: 58.
4. The method of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable domain of SEQ ID NO: 57 and a light chain variable domain of SEQ ID NO: 58.
5. The method of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain of SEQ ID NO: 80.
6. The method of claim 3 , wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain of SEQ ID NO: 80.
7. The method of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof comprises a light chain of SEQ ID NO: 81.
8. The method of claim 2 , wherein the isolated antibody or antigen-binding fragment thereof comprises a light chain of SEQ ID NO: 81.
9. The method of claim 1 , wherein the isolated antibody or antigen-binding fragment thereof comprises a heavy chain of SEQ ID NO: 80 and a light chain of SEQ ID NO: 81.
10. The method of claim 1 , wherein said immunocompromised mammalian subject is human.
11. The method of claim 4 , wherein said immunocompromised mammalian subject is human.
12. The method of claim 9 , wherein said immunocompromised mammalian subject is human.
13. The method of claim 1 , wherein said isolated antibody or antigen-binding fragment thereof is selected from the group consisting of Fv, Fab, Fab′, and F(ab′)2.
14. The method of claim 1 , wherein said antibody is a full-length antibody.
15. The method of claim 14 , wherein said antibody comprises an Fc variant region.
16. The method of claim 1 , wherein the administering is through intravenous (IV) administration.
17. The method of claim 4 , wherein the administering is through intravenous (IV) administration.
18. The method of claim 9 , wherein the administering is through intravenous (IV) administration.
19. The method of claim 10 , wherein the administering is through intravenous (IV) administration.
20. The method of claim 11 , wherein the administering is through intravenous (IV) administration.
21. The method of claim 12 , wherein the administering is through intravenous (IV) administration.