Human rhinovirus (HRV) antibodies
The invention provides isolated fully human monoclonal anti-HRV antibodies, as well as method of making and using these antibodies. Anti-HRV antibodies of the invention prevent or treat subjects having HRV-infections, and related diseases, including, but not limited to, the common cold, nasopharyngitis, croup, pneumonia, bronchiolitis, asthma, chronic obstructive pulmonary disease (COPD), sinusitis, bacterial superinfection, and cystic fibrosis.
1. An isolated fully human monoclonal antibody, wherein said monoclonal antibody has the following characteristics
a) binds to an epitope in the rhinovirus capsid protein selected from the group consisting of VP1, VP2, VP3, and VP4;
b) binds to rhinovirus inside infected cells; and
c) binds to rhinovirus
wherein the antibody comprises,
(a) a VH CDR1 region comprising the amino acid sequence of DFYWT (SEQ ID NO: 5); a VH CDR2 region comprising the amino acid sequence of EIDRDGATYYNPSLKS (SEQ ID NO: 6); a VH CDR3 region comprising the amino acid sequence of RPMLRGVWGNFRSNWFDP (SEQ ID NO: 7); a VL CDR1 region comprising the amino acid sequence of SGSSSNIGYSYVS (SEQ ID NO: 14); a VL CDR2 region comprising the amino acid sequence of ENNKRPS (SEQ ID NO: 15); and a VL CDR3 region comprising the amino acid sequence of GTWDTRLFGGV (SEQ ID NO: 16);
(b) a VH CDR1 region comprising the amino acid sequence of DFAMH (SEQ ID NO: 21); a VH CDR2 region comprising the amino acid sequence of SISRDGSTKYSGDSVKG (SEQ ID NO: 22); a VH CDR3 region comprising the amino acid sequence of DSPYYLDIVGYRYFHHYGMDV (SEQ ID NO: 23); a VL CDR1 region comprising the amino acid sequence of RASQILHSYNLA (SEQ ID NO: 30); a VL CDR2 region comprising the amino acid sequence of GAYNRAS (SEQ ID NO: 31); and a VL CDR3 region comprising the amino acid sequence of QQYGDSPSPGLT (SEQ ID NO: 32);
(c) a VH CDR1 region comprising the amino acid sequence of QNDYHWA (SEQ ID NO: 37); a VH CDR2 region comprising the amino acid sequence of SVHYRQKSYYSPSLKS (SEQ ID NO: 38); a VH CDR3 region comprising the amino acid sequence of HNREDYYDSNAYFDE (SEQ ID NO: 39); a VL CDR1 region comprising the amino acid sequence of SGDDLENTLVC (SEQ ID NO: 46); a VL CDR2 region comprising the amino acid sequence of QDSKRPS (SEQ ID NO: 47); and a VL CDR3 region comprising the amino acid sequence of QTWHRSTAQYV (SEQ ID NO: 48); or
(d) a VH CDR1 region comprising the amino acid sequence of SNDQYWA (SEQ ID NO: 53); a VH CDR2 region comprising the amino acid sequence of SVHYRRRNYYSPSLES (SEQ ID NO: 54); a VH CDR3 region comprising the amino acid sequence of HNWEDYYESNAYFDY (SEQ ID NO: 55); a VL CDR1 region comprising the amino acid sequence of SGDQLENTFVC (SEQ ID NO: 62); a VL CDR2 region comprising the amino acid sequence of QGSKRPS (SEQ ID NO: 63); and a VL CDR3 region comprising the amino acid sequence of QAWDRSTAHYV (SEQ ID NO: 64).
2. An isolated fully human monoclonal antibody, wherein said monoclonal antibody has the following characteristics
a) binds to an epitope in the rhinovirus capsid protein selected from the group consisting of VP1, VP2, VP3, and VP4;
b) binds to rhinovirus inside infected cells; and
c) binds to rhinovirus having serotypes from one or more clades selected from the group consisting of Glade A (major group), Glade A (minor group), Glade B, and Glade D
wherein the antibody comprises,
(a) a VH CDR1 region comprising the amino acid sequence of DFAMH (SEQ ID NO: 21); a VH CDR2 region comprising the amino acid sequence of SISRDGSTKYSGDSVKG (SEQ ID NO: 22); a VH CDR3 region comprising the amino acid sequence of DSPYYLDIVGYRYFHHYGMDV (SEQ ID NO: 23); a VL CDR1 region comprising the amino acid sequence of RASQILHSYNLA (SEQ ID NO: 30); a VL CDR2 region comprising the amino acid sequence of GAYNRAS (SEQ ID NO: 31); and a VL CDR3 region comprising the amino acid sequence of QQYGDSPSPGLT (SEQ ID NO: 32); or
(b) a VH CDR1 region comprising the amino acid sequence of QNDYHWA (SEQ ID NO: 37); a VH CDR2 region comprising the amino acid sequence of SVHYRQKSYYSPSLKS (SEQ ID NO: 38); a VH CDR3 region comprising the amino acid sequence of HNREDYYDSNAYFDE (SEQ ID NO: 39); a VL CDR1 region comprising the amino acid sequence of SGDDLENTLVC (SEQ ID NO: 46); a VL CDR2 region comprising the amino acid sequence of QDSKRPS (SEQ ID NO: 47); and a VL CDR3 region comprising the amino acid sequence of QTWHRSTAQYV (SEQ ID NO: 48); or
(c) a VH CDR1 region comprising the amino acid sequence of SNDQYWA (SEQ ID NO: 53); a VH CDR2 region comprising the amino acid sequence of SVHYRRRNYYSPSLES (SEQ ID NO: 54); a VH CDR3 region comprising the amino acid sequence of HNWEDYYESNAYFDY (SEQ ID NO: 55); a VL CDR1 region comprising the amino acid sequence of SGDQLENTFVC (SEQ ID NO: 62); a VL CDR2 region comprising the amino acid sequence of QGSKRPS (SEQ ID NO: 63); and
a VL CDR3 region comprising the amino acid sequence of QAWDRSTAHYV (SEQ ID NO: 64).
3. An isolated anti-HRV antibody, wherein said antibody comprises,
a VH CDR1 region comprising the amino acid sequence of DFYWT (SEQ ID NO: 5);
a VH CDR2 region comprising the amino acid sequence of EIDRDGATYYNPSLKS (SEQ ID NO: 6);
a VH CDR3 region comprising the amino acid sequence of RPMLRGVWGNFRSNWFDP (SEQ ID NO: 7);
a VL CDR1 region comprising the amino acid sequence of SGSSSNIGYSYVS (SEQ ID NO: 14);
a VL CDR2 region comprising the amino acid sequence of ENNKRPS (SEQ ID NO: 15); and
a VL CDR3 region comprising the amino acid sequence of GTWDTRLFGGV (SEQ ID NO: 16).
4. An isolated anti-HRV antibody, wherein said antibody comprises,
a VH CDR1 region comprising the amino acid sequence of DFAMH (SEQ ID NO: 21);
a VH CDR2 region comprising the amino acid sequence of SISRDGSTKYSGDSVKG (SEQ ID NO: 22);
a VH CDR3 region comprising the amino acid sequence of DSPYYLDIVGYRYFHHYGMDV (SEQ ID NO: 23);
a VL CDR1 region comprising the amino acid sequence of RASQILHSYNLA (SEQ ID NO: 30);
a VL CDR2 region comprising the amino acid sequence of GAYNRAS (SEQ ID NO:
31); and
a VL CDR3 region comprising the amino acid sequence of QQYGDSPSPGLT (SEQ ID NO: 32).
5. An isolated anti-HRV antibody, wherein said antibody comprises,
a VH CDR1 region comprising the amino acid sequence of QNDYHWA (SEQ ID NO: 37);
a VH CDR2 region comprising the amino acid sequence of SVHYRQKSYYSPSLKS (SEQ ID NO: 38);
a VH CDR3 region comprising the amino acid sequence of HNREDYYDSNAYFDE (SEQ ID NO: 39);
a VL CDR1 region comprising the amino acid sequence of SGDDLENTLVC (SEQ ID NO: 46);
a VL CDR2 region comprising the amino acid sequence of QDSKRPS (SEQ ID NO: 47); and
a VL CDR3 region comprising the amino acid sequence of QTWHRSTAQYV (SEQ ID NO: 48).
6. An isolated anti-HRV antibody, wherein said antibody comprises,
a VH CDR1 region comprising the amino acid sequence of SNDQYWA (SEQ ID NO: 53);
a VH CDR2 region comprising the amino acid sequence of SVHYRRRNYYSPSLES (SEQ ID NO: 54);
a VH CDR3 region comprising the amino acid sequence of HNWEDYYESNAYFDY (SEQ ID NO: 55);
a VL CDR1 region comprising the amino acid sequence of SGDQLENTFVC (SEQ ID NO: 62);
a VL CDR2 region comprising the amino acid sequence of QGSKRPS (SEQ ID NO: 63); and
a VL CDR3 region comprising the amino acid sequence of QAWDRSTAHYV (SEQ ID NO: 64).
7. An antibody that binds the same epitope as an antibody comprising,
(a) a VH CDR1 region comprising the amino acid sequence of DFYWT (SEQ ID NO: 5); a VH CDR2 region comprising the amino acid sequence of EIDRDGATYYNPSLKS (SEQ ID NO: 6); a VH CDR3 region comprising the amino acid sequence of RPMLRGVWGNFRSNWFDP (SEQ ID NO: 7); a VL CDR1 region comprising the amino acid sequence of SGSSSNIGYSYVS (SEQ ID NO: 14); a VL CDR2 region comprising the amino acid sequence of ENNKRPS (SEQ ID NO: 15); and a VL CDR3 region comprising the amino acid sequence of GTWDTRLFGGV (SEQ ID NO: 16);
(b) a VH CDR1 region comprising the amino acid sequence of DFAMH (SEQ ID NO: 21); a VH CDR2 region comprising the amino acid sequence of SISRDGSTKYSGDSVKG (SEQ ID NO: 22); a VH CDR3 region comprising the amino acid sequence of DSPYYLDIVGYRYFHHYGMDV (SEQ ID NO: 23); a VL CDR1 region comprising the amino acid sequence of RASQILHSYNLA (SEQ ID NO: 30); a VL CDR2 region comprising the amino acid sequence of GAYNRAS (SEQ ID NO: 31); and a VL CDR3 region comprising the amino acid sequence of QQYGDSPSPGLT (SEQ ID NO: 32);
(c) a VH CDR1 region comprising the amino acid sequence of QNDYHWA (SEQ ID NO: 37); a VH CDR2 region comprising the amino acid sequence of SVHYRQKSYYSPSLKS (SEQ ID NO: 38); a VH CDR3 region comprising the amino acid sequence of HNREDYYDSNAYFDE (SEQ ID NO: 39); a VL CDR1 region comprising the amino acid sequence of SGDDLENTLVC (SEQ ID NO: 46); a VL CDR2 region comprising the amino acid sequence of QDSKRPS (SEQ ID NO: 47); and a VL CDR3 region comprising the amino acid sequence of QTWHRSTAQYV (SEQ ID NO: 48); or
(d) a VH CDR1 region comprising the amino acid sequence of SNDQYWA (SEQ ID NO: 53); a VH CDR2 region comprising the amino acid sequence of SVHYRRRNYYSPSLES (SEQ ID NO: 54); a VH CDR3 region comprising the amino acid sequence of HNWEDYYESNAYFDY (SEQ ID NO: 55); a VL CDR1 region comprising the amino acid sequence of SGDQLENTFVC (SEQ ID NO: 62); a VL CDR2 region comprising the amino acid sequence of QGSKRPS (SEQ ID NO: 63); and a VL CDR3 region comprising the amino acid sequence of QAWDRSTAHYV (SEQ ID NO: 64).
8. An isolated monoclonal anti-HRV antibody comprising,
a) a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 4 and a light chain sequence comprising amino acid sequence SEQ ID NO: 13, or
b) a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 20 and a light chain sequence comprising amino acid sequence SEQ ID NO: 29, or
c) a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 36 and a light chain sequence comprising amino acid sequence SEQ ID NO: 45, or
d) a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 52 and a light chain sequence comprising amino acid sequence SEQ ID NO: 61.
9. A composition comprising an isolated anti-HRV antibody of any one of claims 1 - 8 .
10. A pharmaceutical composition comprising at least one antibody as recited in any one of claims 1 - 8 , and a pharmaceutically acceptable carrier.
11. The composition of claim 9 , further comprising a second therapeutic agent.
12. The composition of claim 11 , wherein the second therapeutic agent is a second antibody, an antiviral drug, an antibiotic, a bronchodilator, a leukotriene blocker, a steroid, an antiflammatory drug, or an oxygen therapy.
13. The composition of claim 12 , wherein the second antibody is specific for human rhinovirus, influenza, parainfluenza, coronavirus, adenovirus, respiratory syncytical virus, picornavirus, metapneumovirus, or anti-IgE antibody.
14. The composition of claim 12 , wherein the anti-viral drug is an entry inhibitor, a fusion inhibitor, an integrase inhibitor, a nucleoside analog, a protease inhibitor, or a reverse transcriptase inhibitor.
15. The composition of claim 12 , wherein the anti-viral drug is Abacavir, Acicolvir, Acyclovir, Adefovir, Amantadine, Amprenavir, Ampligen, Arbidol, Atazanavir, Atripla, Boceprevir, Cidofovir, Combivir, Darunavir, Delavirdine, Didanosine, Docosanol, Edoxudine, Efavirenz, Emtricitabine, Enfuvirtide, Entecavir, Famciclovir, Fomivirsen, Fosamprenavir, Foscarnet, Fosfonet, Ganciclovir, Ibacitabine, Immunovir, Idoxuridine, Imiquimod, Indinavir, Inosine, Interferon (Type I, II, or III), Lamivudine, Lopinavir, Loviride, Maraviroc, Moroxydine, Methisazone, Nelfinavir, Nevirapine, Nexavir, Oseltamivir, Peginterferon alpha-2a, Pencicolvir, Peramivir, Pleconaril, Podophyllotoxin, Raltegravir, Ribavirin, Rimantadine, Ritonavir, Pyramidine, Saquinavir, Stavudine, Tea tree oil, Tenofovir, Tenofovir disoproxil, Tipranavir, Trifluridine, Trizivir, Tromantadine, Truvada, Valaciclovir, Valganciclovir, Vicriviroc, Vidarabine, Viramidine, Zalcitabine, Zanamivir, or Zidovudine.
16. The composition of claim 12 , wherein the antibiotic is an Aminoglycoside, a Carbapenem, a Cephalosporin, a Lincosamide, a Macrolide, a Penicillin, or a Quinolone.
17. The composition of claim 12 , wherein the antibiotic is Amikacin, Gentamicin, Kanamycin, Neomycin, Netilmycin, Tobramycin, Paromycin, Geldanamycin, Ertapenem, Dorpenem, Imipenem/Cilastatin, Meropenem, Cefadroxil, Cefazolin, Cefalotin, Cefalothin, Cefalexin, Cefaclor, Ceamandole, Cefoxitin, Cefprozil, Cefurozime, Cefixime, Cefdinir, Defditoren, Cefoperazone, Cefotaxime, Cefazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Ceftobiprole, Teicoplanin, Vancomycin, Telavancin, Clindamycin, Lincomycin, Daptomycin, Azithromyzin, Clarithromycin, Dirithromycin, Erythromycin, Roxithromycin, Troleandomycin, Spectinomycin, Aztreonam, Furazolidone, Nitofurantoin, Amoxicillin, Ampicillin, Azlocillin, Carbenicillin, Cloxacillin, Dicloxacillin, Flucloxacillin, Mezlocillin, Methicillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin, Temocillin, Ticarcillin, Amoxicillin/clavulanate, Ampicillin/sulbactam, Piperacillin/tazobactam, Ticarcillin/clavulanate, Bacitracin, Colistin, Polymyxin B, Ciprofloxacin, Enoxacin, Gatifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin, Trovafloxacin, Grepafloxacin, Sparfloxacin, Temafloxacin, Mafenide, Sulfonamidochrysoidine, Sulfacetamide, Sulfadiazine, Silver sulfadiazine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Trimethoprim, Trimethoprim-Sulfamethoxazole (Co-trumoxazole), Demeclocycline, Docycline, Minocycline, Oxytetracycline, Tetracycline, Clofazimine, Dapsone, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Pyrazinamide, Rifampicin, Rifampin, Rifabutin, Rifapentin, Stretomycin, Arsphenamine, Choramphenicol, Fosfomycin, Fusidic acid, Linezolid, Metonidazole, Mupirocin, Platensimycin, Quinupristin/Dalfopristin, Rifaximin, Thamphenicol, Tigecycline, Tinidazole.
18. The composition of claim 12 , wherein the bronchodilator is a short- or long-acting agent.
19. The composition of claim 12 , wherein the short-acting bronchodilator is a β2-agonist or an anticholinergic.
20. The composition of claim 18 , wherein the long-acting bronchodilator is a β2-agonist or a theophylline.
21. The composition of claim 12 , wherein the steroid is a corticosteroid.
22. The composition of claim 21 , wherein corticosteroid is hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, prednisone, triamcinolone acetonide, triamcinolone alcohol, mometasone, amcinonide, budesonide, desonide, fluocinonide, fluocinolone acetonide, halcinonide, betamethasone, betamethasone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, fluocortolone, hydrocortisone-17-butyrate, hydrocortisone-17-valerate, aclometasone dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone-17-butyrate, clobetasol-17-propionate, fluocortolone caproate, fluocortolone pivalate, and fluprednidene acetate.
23. The composition of claim 12 , wherein the anti-inflammatory drug is an antihistamine or a histamine receptor blocker.
24. The composition of claim 12 , wherein the oxygen therapy is supplemental oxygen gas, and wherein the arterial blood oxygen saturation of the subject following treatment is greater than or equal to 85%.
25. A vaccine comprising an isolated anti-HRV antibody as recited in any one of claims 1 - 8 .
26. A kit comprising an isolated anti-HRV antibody as recited in any one of claims 1 - 8 .
27. The antibody of one of claims 1 - 8 , wherein the antibody binds to an epitope comprising a portion of two or more rhinovirus capsid proteins selected from the group consisting of VP1, VP2, VP3, and VP4.
28. The antibody of any one of claims 1 , 3 , 4 , 5 , 6 , 7 and 8 , wherein the antibody binds to rhinovirus serotypes from one or more clades selected from the group consisting of Glade A (major group), Glade A (minor group), Glade B, and Glade D.
29. The antibody of any one of claims 1 - 8 , wherein the antibody cross-neutralizes multiple rhinovirus serotypes from the group consisting of Glade A (major group), Glade A (minor group), Glade B, and Glade D.
30. The antibody of any one of claims 1 - 8 , wherein the antibody neutralizes at least 40% of HRV serotypes selected from the group consisting of HRV-12, HRV-13, HRV-16, HRV-21, HRV-23, HRV-24, HRV-28, HRV-34, HRV-36, HRV-38, HRV-40, HRV-51, HRV-54, HRV-61, HRV-63, HRV-64, HRV-67, HRV-74, HRV-75, HRV-76, HRV-88, HRV-89, HRV-29, HRV-31, HRV-49, HRV-62, HRV-14, HRV-26, HRV-37, HRV-48, HRV-52, HRV-70, HRV-83, HRV-84, HRV-86, HRV-93, HRV-08, and HRV-45.
31. The antibody of any one of claims 1 - 8 , wherein the antibody binds to at least 90% of the HRV serotypes.
32. The antibody of claim 28 , wherein the antibody neutralizes the HRV serotypes with a median IC50 value of equal to or less than 100 ng/ml.
33. The antibody of any one of claims 1 - 8 , wherein the antibody is isolated from a B-cell from a human donor.
34. The antibody of any one of claims 1 - 8 , wherein said epitope is non-linear.
35. The composition of claim 10 , further comprising a second therapeutic agent.
36. The composition of claim 35 , wherein the second therapeutic agent is a second antibody, an antiviral drug, an antibiotic, a bronchodilator, a leukotriene blocker, a steroid, an antiflammatory drug, or an oxygen therapy.
37. The composition of claim 36 , wherein the second antibody is specific for human rhinovirus, influenza, parainfluenza, coronavirus, adenovirus, respiratory syncytical virus, picornavirus, metapneumovirus, or anti-IgE antibody.
38. The composition of claim 36 , wherein the anti-viral drug is an entry inhibitor, a fusion inhibitor, an integrase inhibitor, a nucleoside analog, a protease inhibitor, or a reverse transcriptase inhibitor.
39. The composition of claim 36 , wherein the anti-viral drug is Abacavir, Acicolvir, Acyclovir, Adefovir, Amantadine, Amprenavir, Ampligen, Arbidol, Atazanavir, Atripla, Boceprevir, Cidofovir, Combivir, Darunavir, Delavirdine, Didanosine, Docosanol, Edoxudine, Efavirenz, Emtricitabine, Enfuvirtide, Entecavir, Famciclovir, Fomivirsen, Fosamprenavir, Foscarnet, Fosfonet, Ganciclovir, Ibacitabine, Immunovir, Idoxuridine, Imiquimod, Indinavir, Inosine, Interferon (Type I, II, or III), Lamivudine, Lopinavir, Loviride, Maraviroc, Moroxydine, Methisazone, Nelfinavir, Nevirapine, Nexavir, Oseltamivir, Peginterferon alpha-2a, Pencicolvir, Peramivir, Pleconaril, Podophyllotoxin, Raltegravir, Ribavirin, Rimantadine, Ritonavir, Pyramidine, Saquinavir, Stavudine, Tea tree oil, Tenofovir, Tenofovir disoproxil, Tipranavir, Trifluridine, Trizivir, Tromantadine, Truvada, Valaciclovir, Valganciclovir, Vicriviroc, Vidarabine, Viramidine, Zalcitabine, Zanamivir, or Zidovudine.
40. The composition of claim 36 , wherein the antibiotic is an Aminoglycoside, a Carbapenem, a Cephalosporin, a Lincosamide, a Macrolide, a Penicillin, or a Quinolone.
41. The composition of claim 36 , wherein the antibiotic is Amikacin, Gentamicin, Kanamycin, Neomycin, Netilmycin, Tobramycin, Paromycin, Geldanamycin, Ertapenem, Dorpenem, Imipenem/Cilastatin, Meropenem, Cefadroxil, Cefazolin, Cefalotin, Cefalothin, Cefalexin, Cefaclor, Ceamandole, Cefoxitin, Cefprozil, Cefurozime, Cefixime, Cefdinir, Defditoren, Cefoperazone, Cefotaxime, Cefazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Ceftobiprole, Teicoplanin, Vancomycin, Telavancin, Clindamycin, Lincomycin, Daptomycin, Azithromyzin, Clarithromycin, Dirithromycin, Erythromycin, Roxithromycin, Troleandomycin, Spectinomycin, Aztreonam, Furazolidone, Nitofurantoin, Amoxicillin, Ampicillin, Azlocillin, Carbenicillin, Cloxacillin, Dicloxacillin, Flucloxacillin, Mezlocillin, Methicillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin, Temocillin, Ticarcillin, Amoxicillin/clavulanate, Ampicillin/sulbactam, Piperacillin/tazobactam, Ticarcillin/clavulanate, Bacitracin, Colistin, Polymyxin B, Ciprofloxacin, Enoxacin, Gatifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin, Trovafloxacin, Grepafloxacin, Sparfloxacin, Temafloxacin, Mafenide, Sulfonamidochrysoidine, Sulfacetamide, Sulfadiazine, Silver sulfadiazine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Trimethoprim, Trimethoprim-Sulfamethoxazole (Co-trumoxazole), Demeclocycline, Docycline, Minocycline, Oxytetracycline, Tetracycline, Clofazimine, Dapsone, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Pyrazinamide, Rifampicin, Rifampin, Rifabutin, Rifapentin, Stretomycin, Arsphenamine, Choramphenicol, Fosfomycin, Fusidic acid, Linezolid, Metonidazole, Mupirocin, Platensimycin, Quinupristin/Dalfopristin, Rifaximin, Thamphenicol, Tigecycline, Tinidazole.
42. The composition of claim 36 , wherein the bronchodilator is a short- or long-acting agent.
43. The composition of claim 42 , wherein the short-acting bronchodilator is a β2-agonist or an anticholinergic.
44. The composition of claim 42 , wherein the long-acting bronchodilator is a β2-agonist or a theophylline.
45. The composition of claim 36 , wherein the steroid is a corticosteroid.
46. The composition of claim 45 , wherein corticosteroid is hydrocortisone, hydrocortisone acetate, cortisone acetate, tixocortol pivalate, prednisolone, methylprednisolone, prednisone, triamcinolone acetonide, triamcinolone alcohol, mometasone, amcinonide, budesonide, desonide, fluocinonide, fluocinolone acetonide, halcinonide, betamethasone, betamethasone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, fluocortolone, hydrocortisone-17-butyrate, hydrocortisone-17-valerate, aclometasone dipropionate, betamethasone valerate, betamethasone dipropionate, prednicarbate, clobetasone-17-butyrate, clobetasol-17-propionate, fluocortolone caproate, fluocortolone pivalate, and fluprednidene acetate.
47. The composition of claim 36 , wherein the anti-inflammatory drug is an antihistamine or a histamine receptor blocker.
48. The composition of claim 36 , wherein the oxygen therapy is supplemental oxygen gas, and wherein the arterial blood oxygen saturation of the subject following treatment is greater than or equal to 85%.