Nanoparticulate CpG Immunotherapy in RAO-Affected Horses: Phase I and IIa Study

Journal of Veterinary Internal Medicine

Volumn 29, Issue 1, 2015, Pages 286-293

  Klier, J ^a   Lehmann, B ^a   Fuchs, S ^a   Reese, S ^a   Hirschmann, A ^a   Coester, C ^a   Winter, G ^a   Gehlen, H ^a,b  

^a UNIVERSITY OF MUNICH   (Germany)

^b FREIE UNIVERSITÄT BERLIN   (Germany)

Author keywords

RAO; Gelatin nanoparticle; Immunotherapy; Inhalation

Indexed keywords

ANIMALIA; EQUIDAE;

NANOPARTICLE; OLIGODEOXYRIBONUCLEOTIDE; OXYGEN;

ANIMAL; AUSCULTATION; BLOOD; BREATHING; CLINICAL TRIAL; CONTROLLED STUDY; DRUG EFFECTS; FEMALE; HORSE; HORSE DISEASES; LUNG; LUNG DISEASES, OBSTRUCTIVE; MALE; MUCUS; PATHOLOGY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; PRESSURE; RANDOMIZED CONTROLLED TRIAL; VETERINARY;

ANIMALS; AUSCULTATION; FEMALE; HORSE DISEASES; HORSES; LUNG; LUNG DISEASES, OBSTRUCTIVE; MALE; MUCUS; NANOPARTICLES; OLIGODEOXYRIBONUCLEOTIDES; OXYGEN; PARTIAL PRESSURE; RESPIRATION;

EID: 84921485388     PISSN: 08916640     EISSN: 19391676     Source Type: Journal    
DOI: 10.1111/jvim.12524     Document Type: Article

References (35)

1. Robinson NE. Recurrent airway obstruction (Heaves). In: Lekeux P, ed. Equine Respiratory Diseases. Ithaca, New York: International Veterinary Information Service; 2001 [http://www.ivis.org/special_books/Lekeux/ robinson/chapter_frm.asp?LA=1]
2. Neuhaus S, Bruendler P, Frey CF, et al. Increased parasite resistance and recurrent airway obstruction in horses of a high-prevalence family. J Vet Intern Med 2010;24:407-413.
3. Lunn P, Horohov D. The equine immune system. In: Reed SM, Bayly WM, Sellon DC, eds. Equine Internal Medicine, 3rd ed. St. Louis: Saunders Elsevier; 2010:2-56.
4. Kirschvink N, Reinhold P. Use of alternative animals as asthma models. Curr Drug Targets 2008;9:470-484.
5. Millerick-May ML, Karmaus W, Derksen FJ, et al. Particle mapping in stables at an American Thoroughbred racetrack. Equine Vet J 2011;43:599-607.
6. Gerber V, Baleri D, Klukowska-Rötzler J, et al. Mixed inheritance of equine recurrent airway obstruction. J Vet Intern Med 2009;23:626-630.
7. Künzle F, Gerber V, Van Der Haegen A, et al. IgE-bearing cells in bronchoalveolar lavage fluid and allergen-specific IgE levels in sera from RAO-affected horses. J Vet Med A 2007;54:40-47.
8. Ainsworth DM, Cheetham J. Disorders of the respiratory system. In: Reed SM, Bayly WM, Sellon DC, eds. Equine Internal Medicine, 3rd ed. St. Louis: Saunders Elsevier; 2010:340-344.
9. Moran G, Folch H. Recurrent airway obstruction in horses-An allergic inflammation: A review. Vet Med - Czech 2011;56:1-13.
10. Fonseca D, Kline J. Use of CpG oligonucleotides in treatment of RAO and allergic disease. Adv Drug Deliv Rev 2009;61:256-262.
11. Vollmer J, Krieg AM. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv Drug Deliv Rev 2009;61:195-204.
12. Schneberger D, Caldwell S, Singh Suri S, et al. Expression of toll-like receptor 9 in horse lungs. Anat Rec 2009;292:1068-1077.
13. Wilson KD, de Jong SD, Tam YK. Lipid-based delivery of CpG oligonucleotides enhances immunotherapeutic efficacy. Adv Drug Deliv Rev 2009;61:233-242.
14. Bourquin C, Anz D, Zwiorek K, et al. Targeting CpG oligodeoxynucleotides to the lymph node by nanoparticles elicits efficient antitumoral immunity. J Immunol 2008;181:2990-2998.
15. Zwiorek K, Bourquin C, Battiany J, et al. Delivery by cationic gelatin nanoparticles strongly increases the immunostimulatory effects of CpG oligonucleotides. Pharm Res 2008;25:551-562.
16. Brzoska M, Langer K, Coester C, et al. Incorporation of biodegradable nanoparticles into human airway epithelium cells-in vitro study of the suitability as a vehicle for drug or gene delivery in pulmonary diseases. Biochem Biophys Res Commun 2004;318:562-570.
17. Tseng C-L, Yueh-Hsiu WuS, Wang W-H, et al. Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatine nanoparticles administered via aerosol delivery in nude mice with lung cancer. Biomaterials 2008;29:3014-3022.
18. Tseng C-L, Su W-Y, Yen K-C, et al. The use of biotinylated-EGF-modified gelatine nanoparticle carrier to enhance cisplatin accumulation in cancerous lungs via inhalation. Biomaterials 2009;30:3476-3485.
19. Fuchs S, Klier J, May A, et al. Towards an inhalative in vivo application of immunomodulating gelatin nanoparticles in horse-related preformulation studies. J Microencapsul 2012;29:615-625.
20. Senti G, Johansen P, Haug S, et al. Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: A phase I/IIa clinical trial. Clin Exp Allergy 2009;39:562-570.
21. Mueller RS, Veir J, Fieseler KV, Dow SW. Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific immunotherapy of dogs with refractory atopic dermatitis-A pilot study. Vet Dermatol 2005;16:61-68.
22. Hullmann AG. Prophylaxe der Rhodococcus equi-Pneumonie bei Fohlen durch Vakzination mit Rhodococcus equi-Impfstoff und Adjuvans CpG XXXX. School of Veterinary Medicine Hannover; 2006. Thesis.
23. Lopez AM, Hecker R, Mutwiri G, et al. Formulation with CpG ODN enhances antibody responses to an equine influenza virus vaccine. Vet Immunol Immunopathol 2006;114:103-110.
24. Liu T, Nerren J, Murrell J, et al. CpG-induced stimulation of cytokine expression by peripheral blood mononuclear cells of foals and their dams. J Jevs 2008;28:419-426.
25. Liu T, Nerren J, Liu M, et al. Basal and stimulus-induced cytokine expression is selectively impaired in peripheral blood mononuclear cells of newborn foals. Vaccine 2009;27:674-683.
26. Klier J, Fuchs S, May A, et al. A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses. Pharm Res 2012;29:1650-1657.
27. Robinson NE. International workshop on equine chronic airway disease. Michigan State University. Equine Vet J 2001;33:5-19.
28. Gerber V, King M, Schneider DA, Robinson NE. Tracheobronchial mucus viscoelasticity during environmental challenge in horses with recurrent airway obstruction. Equine Vet J 2000;32:411-417.
29. Grabner A. Arterielle Blutgasanalyse. In: Kraft W, Dürr UM, eds. Klinische Labordiagnostik in der Tiermedizin, 6th ed. Stuttgart: Schattauer; 2005:429-430.
30. Gerber V, Straub R, Marti E, et al. Endoscopic scoring of mucus quantity and quality: Observer and horse variance and relationship to inflammation, mucus viscoelasticity and volume. Equine Vet J 2004;36:576-582.
31. Deegen E, Klein HJ. Interpleuraldruckmessungen und Bronchospasmolysetests mit einem portalen Ösophagusdruckmessgerät. Pferdeheilkunde 1987;21:213-221.
32. Klier J, May A, Fuchs S, et al. Immunostimulation of bronchoalveolar lavage cells from recurrent airway obstruction-affected horses by different CpG-classes bound to gelatin nanoparticles. Vet Immunol Immunopathol 2011;144:79-87.
33. Mutwiri GK, Nichani AK, Babiuk S, et al. Strategies for enhancing the immunostimulatory effects of CpG oligodeoxynucleotides. J Control Release 2004;97:1-17.
34. Nakagawa S, Cuthill I.C. Effect size, confidence interval and statistical significance: A practical guide for biologist. Biol Rev 2007;82:591-605.
35. Klier J. Neuer Therapieansatz zur Behandlung der COB des Pferdes durch Immunstimulation von BAL-Zellen mit verschiedenen CpG-Klassen. Munich: School of Veterinary Medicine, Ludwig-Maximilians University; 2011. Thesis.