COMPOSITIONS AND METHODS FOR THE TREATMENT AND PREVENTION OF Ebp PILUS-RELATED DISEASES

• US 20180055923A1
• Filed: 11/13/2017
• Published: 03/01/2018
• Est. Priority Date: 09/12/2014
• Status: Active Grant

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Hultgren, Scott J., Caparon, Michael G., Pinkner, Jerome, Flores-Mireles, Ana L.
• Granted Patent: US 10,449,242 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/55566 Emulsions, e.g. Freund's adjuvant, MF59
• CPC Class Codes: A61K 39/09 Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
• CPC Class Codes: C07K 16/1267 from Gram-positive bacteria

Abstract

The present invention relates to compositions comprising EbpA and methods of use thereof. Specifically, methods useful in the treatment and prevention of EbpA-associated infections.

Claims

1. A method of treating an EbpA-associated infection in a subject, the method comprising administering to the subject one or more of an effective amount of a vaccine composition comprising SEQ ID NO:

3, an effective amount of a composition comprising an anti-EbpA antibody, or combinations thereof.

2. The method of claim 1, wherein the EbpA-associated infection is a catheter-associated urinary tract infection (CAUTI).

3. The method of claim 2, wherein the CAUTI is Enterococcus mediated.

4. The method of claim 3, wherein the Enterococcus is E. faecalis.

5. The method of claim 1, wherein the vaccine composition is administered at a dose ranging from 0.3 to 100 μ

g.

6. The method of claim 1, wherein the vaccine composition or anti-EbpA antibody is administered every 2 to 4 weeks.

7. The method of claim 1, wherein the vaccine composition or anti-EbpA antibody is administered intramuscularly.

8. The method of claim 1, further comprising administering an antimicrobial agent.

9. The method of claim 1, wherein the vaccine composition or anti-EbpA antibody disrupts the interaction between EbpA and fibrinogen.

10. The method of claim 1, wherein the vaccine compostion comprises more than one SEQ ID NO:

3 linked together.

11. The method of claim 1, wherein SEQ ID NO:

3 comprises a fibrinogen-binding domain.

12. The method of claim 1, wherein the vaccine composition comprises an immune effective amount of adjuvant selected from the group consisting of an aluminum salt, calcium salt, iron, zinc, acylated tyrosine, acylated sugars, saccharide, polyphoshazenes, biodegradable microspheres, monophosporyl lipid A, lipid A derivatives quit A, Saponin, QS21, Freund'"'"'s Incomplete Adjuvant, Merck Adjuvant 65, AS-2, CpG oligonucleotides, bioadhesives and mucoadhesives, microparticles, liposomes, polyoxyethyene ether formulations, polyoxyethylene ester formulations, muramyl peptides or imidazoquinolone compounds.

13. A method for detecting an EbpA-associated infection, the method comprising:

a) obtaining a biological sample from a subject;

b) measuring the amount of EbpA NTD in the sample using an anti-EbpA NTD antibody;

c) comparing the amount of EbpA NTD in the sample to a reference value; and

d) classifying the subject as having a high or low amount of EbpA NTD based on the amount of EbpA NTD measured in the sample.

14. The method of claim 13, wherein the biological sample is a biological fluid or a medical device or implanted material.

15. The method of claim 13, wherein the EbpA-associated infection is a catheter-associated urinary tract infection (CAUTI).

16. The method of claim 13, wherein when the subject has a high amount of EbpA NTD, an EbpA-associated infection is detected.

17. The method of claim 13, further comprising treating a subject identified as having a high amount of EbpA NTD with antimicrobial therapy, a vaccine composition comprising an EbpA NTD, a composition comprising an anti-EbpA NTD antibody, or combinations thereof.