Methods and compositions for treating respiratory disease
Disclosed herein are methods and nanoparticles suitable for use in reducing exacerbations in COPD patients. The methods and compositions advantageously reduce the incidence of hospitalization in COPD patients that occurs in response to environmental insults such as exposure to or infection by RSV. Dosages, formulations, and methods for preparing the vaccines and nanoparticles are also disclosed.
1. A method of reducing exacerbations of chronic obstructive pulmonary disease (COPD) in a human subject comprising administering a nanoparticle vaccine to the subject, wherein the nanoparticle comprises: a non-ionic detergent core and a viral glycoprotein, wherein the viral glycoprotein is associated with the core and the detergent is present at about 0.03% to about 0.05%, wherein the viral glycoprotein is an RSV F protein.
2. The method of claim 1 , wherein the exacerbation is caused by an environmental insult.
3. The method of claim 2 , wherein the environmental insult is a pathogen.
4. The method of claim 3 , wherein the pathogen is a viral pathogen.
5. The method of claim 4 , wherein the viral pathogen is selected from the group consisting of an RSV virus and an influenza virus.
6. The method of claim 1 , wherein the incidence of exacerbations is reduced by about 50% as determined by hospitalization rate.
7. The method of claim 6 , wherein the human is at least 60 years old.
8. The method of claim 1 , wherein the non-ionic detergent is selected from the group consisting of PS20, PS40, PS60, PS65, and PS80.
9. The method of claim 8 , wherein the RSV F protein is combined with at least one of an influenza HA protein, and an influenza NA protein.
10. The method of claim 1 , wherein the molar ratio of non-ionic detergent to viral glycoprotein is about 30:1 to about 60:1.
11. The method of claim 10 , wherein the RSV F protein comprises a deletion of 1 to 10 amino acids corresponding to amino acids 137-146 of SEQ ID NO:2 and an inactivated primary furin cleavage site corresponding to amino acids 131 to 136 of SEQ ID NO:2, wherein the primary furin cleavage site is inactivated by mutation.
12. The method of claim 11 , wherein the composition is substantially free of any other detergent.
13. The method of claim 11 , wherein the RSV-F protein is selected from the group consisting of SEQ ID NOS:2-13 and variants of SEQ ID NOS:2-13 lacking part or all of the N-terminal signal peptide.
14. The method of claim 13 , wherein the RSV F protein consists of SEQ ID NO:19.
15. The method of claim 14 , wherein the non-ionic detergent is PS80.
16. A method of reducing exacerbations of chronic obstructive pulmonary disease (COPD) in response to an environmental insult in a human having COPD comprising administering an immunogenic composition to the human, wherein the immunogenic composition comprises a first nanoparticle, wherein the first nanoparticle comprises a PS80 non-ionic detergent core and a first viral glycoprotein, wherein the viral glycoprotein is associated with the core and the detergent is present at about 0.03% to about 0.05%, wherein the first viral glycoprotein is an RSV F glycoprotein.
17. The method of claim 16 wherein the RSV-F protein is selected from the group consisting of SEQ ID NOS:2-13 and variants of SEQ ID NOS:2-13 lacking part or all of the N-terminal signal peptide.
18. The method of claim 17 wherein the immunogenic composition comprises a second nanoparticle wherein the second nanoparticle comprises a PS80 non-ionic detergent core and a second viral glycoprotein, wherein the second viral protein is an influenza HA protein.