Detoxified pneumococcal neuraminidase and uses thereof
Provided herein are compositions designed to reduce or prevent pneuomococcal infections, nasal carriage, nasal colonization, and central nervous system invasion. Provided herein is a composition comprising a polypeptide comprising the amino acid sequence of SEQ ID NO: 19 or a variant thereof that can elicit an anti-neuraminidase immune response. Further provided are methods of making and using the compositions disclosed herein. Specifically provided are methods of generating antibodies in a subject comprising administering to the subject an agent or composition taught herein. Also provided are methods of reducing or preventing nasal carriage or pneumococcal infection in a subject comprising administering to the subject a composition taught herein.
1. An antigenic portion of a detoxified pneumococcal neuraminidase, wherein the antigenic portion consists of a sequence with at least 95% sequence identity to SEQ ID NO: 19, wherein the antigenic portion can elicit an anti-neuraminidase immune response.
2. The antigenic portion of the detoxified pneumococcal neuraminidase of claim 1 , wherein the antigenic portion of the detoxified pneumococcal neuraminidase has less than about 60% of the activity of non-detoxified neuraminidase and wherein the non-detoxified neuraminidase is a wild type pneumococcal neuraminidase.
3. The antigenic portion of the detoxified pneumococcal neuraminidase of claim 1 , wherein the antigenic portion of the detoxified pneumococcal neuraminidase has less than about 10% of the activity of non-detoxified neuraminidase and wherein the non-detoxified neuraminidase is a wild type pneumococcal neuraminidase.
4. The antigenic portion of the detoxified pneumococcal neuraminidase of claim 1 , wherein the antigenic portion of the detoxified pneumococcal neuraminidase comprises a deletion of at least 7% of the naturally occurring amino acids of non-detoxified neuraminidase and wherein the non-detoxified neuraminidase is a wild type pneumococcal neuraminidase.
5. The antigenic portion of the detoxified pneumococcal neuraminidase of claim 1 , wherein the antigenic portion consists of the sequence SEQ ID NO: 35.
6. The antigenic portion of the detoxified pneumococcal neuraminidase of claim 1 , wherein the antigenic portion consists of the sequence SEQ ID NO: 36.
7. The antigenic portion of the detoxified pneumococcal neuraminidase of claim 1 , wherein the antigenic portion consists of a sequence with at least 99% sequence identity to SEQ ID NO: 19.
8. A composition comprising (a) an antigenic portion of a detoxified pneumococcal neuraminidase, wherein the antigenic portion consists of a sequence with at least 95% sequence identity to SEQ ID NO: 19, wherein the antigenic portion can elicit an anti-neuraminidase immune response, and (b) a pharmaceutically acceptable carrier.
9. The composition of claim 8 , further comprising an adjuvant.
10. The composition of claim 8 , wherein the antigenic portion consists of the sequence SEQ ID NO: 35 or SEQ ID NO: 36.
11. The composition of claim 8 , wherein the antigenic portion consists of a sequence with at least 99% sequence identity to SEQ ID NO: 19.
12. A composition comprising (a) an antigen portion of a detoxified pneumococcal neuraminidase, wherein the antigenic portion consists of a sequence with at least 95% sequence identity to SEQ ID NO: 19, wherein the antigenic portion can elicit an anti-neuraminidase immune response, and (b) a pharmaceutically acceptable carrier, wherein the composition is suitable for administration to a mucosal surface.
13. The composition of claim 12 , wherein the composition is a nasal spray.
14. The composition of claim 12 , wherein the composition is a nebulizer solution.
15. The composition of claim 12 , wherein the composition is an aerosol inhalant.
16. The composition of claim 12 , wherein the antigenic portion consists of the amino acid sequence SEQ ID NO: 35 or SEQ ID NO: 36.
17. The composition of claim 12 , wherein the antigenic portion consists of a sequence with at least 99% sequence identity to SEQ ID NO: 19.
18. A container comprising the composition of claim 12 .
19. The container of claim 18 , wherein the container is a nasal sprayer.
20. The container of claim 18 , wherein the container is a nebulizer.
21. The container of claim 8 , wherein the container is an inhaler.
22. A method of reducing pneumococcal nasal carriage in a subject comprising administering to the subject a polypeptide consisting of an amino acid sequence with at least 95% sequence identity to SEQ ID NO: 19, wherein the polypeptide can elicit an anti-neuraminidase immune response in the subject, wherein the polypeptide is administered under conditions that reduce the nasal carriage.
23. A method of reducing pneumococcal infection in a subject comprising administering to the subject a polypeptide consisting of a sequence with at least 95% sequence identity to SEQ ID NO: 19, wherein the polypeptide can elicit an anti-neuraminidase immune response in the subject, wherein the polypeptide is administered under conditions that reduce the infection.
24. The method of claim 23 , wherein the pneumococcal infection is meningitis.
25. The method of claim 23 , wherein the pneumococcal infection is otitis media.
26. The method of claim 23 , wherein the pneumococcal infection is pneumonia.
27. The method of claim 23 , wherein the pneumococcal infection is hemolytic uremia.
28. The method of claim 22 , wherein the polypeptide consists of the amino acid sequence SEQ ID NO: 35 or SEQ ID NO: 36.
29. The method of claim 22 , wherein the polypeptide consists of a sequence with at least 99% sequence identity to SEQ ID NO: 19.