圆PLoS|oNE A Pre-Clinical Safety Evaluation of SBP(HBsAg-Binding Protein) 14. Agmon-Levin N, Arango MT, Kivity S, Katzav A, Gilburd B, Blank M, et aL. Immunization with hepatitis B vaccine accelerates SLE-like disease in a murine model. Journal of autoimmunity. 2014: 54: 21-32. doi 10.1016/aut201406006PMD:25042822 15. Moon SH, Shin EC, Noh YW, Lim YT. Evaluation of hyaluronic acid-based combination adjuvant con- aining monophosphoryl lipid a and aluminum salt for hepatitis B vaccine. Vaccine. 2015: 33(38): 4762 9.doi:101016/ vaccine201508006PM|D:26271830 16. Ben Azoun S, Belhaj A. E, Kallel H Rabies virus glycoprotein enhanced expression in Pichia pastoris using the constitutive GAP promoter. Biochemical Engineering JournaL 2016: 113: 77-85. 17. Pane J A, Fleming F. E, Graham K L, et al. Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I inter galling. Scientific Reports 2016: 6: 29697. doi: 10. 1038 srep29697PMD:27405244 18. Segal L, Morelle D, Kaaber K, Destexhe E, Garcon N Non-clinical safety assessment of single and ular administration of a human papillomavirus-16/18 vaccine in rabbits and rat Joumal of applied toxicology. JAT. 2015; 35(12): 1577-85. doi: 10.1002/iat 3131 PMID: 25752809 19. Pujol JL, Vansteenkiste JF, De Pas TM, Atanackovic D, Reck M, Thomeer M, et aL. Safety and Immuno- genicity of MAGE-A3 Cancer Immunotherapeutic with or without Adjuvant Chemotherapy in Patients with Resected Stage IB to Ill MAGE-A3-Positive Non-Small-Cell Lung Cancer. Joumal of thoracic oncology: official publication of the Intemational Association for the Study of Lung Cancer. 2015: 10 20. Minhinnick A, Satti l, Harris S, wilkie M, Sheehan S, Stockdale L, et al. A first-in-human phase 1 trial to uate the safety and immunogenicity of the candidate tuberculosis vaccine MVA85A-lMX313 administered to BCG-vaccinated adults. Vaccine 2016: 34(11): 1412-21. doi: 10. 1016/vaccine 2016. 01062PMD:26854906 21. Belafsky PC, Peake J, Smiley-Jewell SM, Verma SP, Dworkin-Valenti J, Pinkerton KE Soot and house dust mite allergen cause eosinophilic laryngitis in an animal model. The Laryngoscope 2016: 126 (1):108-12.doi:10.1002/any25467PMD:26197967 22. Kimber L, Dearman RJ, Basketter DA, Boverhof DR Chemical respiratory allergy reverse engine an adverse outcome pathway. Toxicology. 2014: 318: 32-9. doi: 10. 1016/ tox. 2014.02.001 PMID 24534103 23. Ghatan PH, Marcusson-Stahl M, Matura M, Bjorkheden C, Lundborg P, Cederbrant K Sensitization to meprazole in the occupational setting. Contact dermatitis. 2014: 71(6): 371-5. doi: 10. 1111/cod. 12305 PMD:25310916 24. Zhai SQ, Yu N, Guo ww, Zhang Y Effect of Binghuang ear drop treatment on otitis externa in guinea pigs. Cell biochemistry and biophysics. 2014: 70(3): 1813-5 do: 10.1007/s12013-014-0134-Y PMID 25. Persson GR, Engel LD, Whitney CW, Weinberg A, Moncla BJ, Darveau RP, et al. Macaca fascicularis as a model in which to assess the safety and efficacy of a vaccine for periodontitis. Oral microbiology and immunology. 1994; 9(2):104 26. Leroux-Roels G, Marchant A, Levy J, Van Damme P, TF, Horsmans Y, et al. Impact of adju- vants on CD4+ T cell and B cell responses to a protein accine:Results from a phase ll,ran- domized, multicenter trial. Clinical immunology 2016: 27.doi:10.1016/cm2016.05007 PM|D:27236001 PLOS ONE DO1: 10. 1371/journal pone. 0170313 January 19, 2017 1/14. Agmon-Levin N, Arango MT, Kivity S, Katzav A, Gilburd B, Blank M, et al. Immunization with hepatitis B vaccine accelerates SLE-like disease in a murine model. Journal of autoimmunity. 2014; 54:21–32. doi: 10.1016/j.jaut.2014.06.006 PMID: 25042822 15. Moon SH, Shin EC, Noh YW, Lim YT. Evaluation of hyaluronic acid-based combination adjuvant con￾taining monophosphoryl lipid A and aluminum salt for hepatitis B vaccine. Vaccine. 2015; 33(38):4762– 9. doi: 10.1016/j.vaccine.2015.08.006 PMID: 26271830 16. Ben Azoun S., Belhaj A. E., Kallel H. Rabies virus glycoprotein enhanced expression in Pichia pastoris using the constitutive GAP promoter. Biochemical Engineering Journal. 2016; 113:77–85. 17. Pane J. A., Fleming F. E., Graham K. L., et al. Rotavirus acceleration of type 1 diabetes in non-obese diabetic mice depends on type I interferon signalling. Scientific Reports. 2016; 6:29697. doi: 10.1038/ srep29697 PMID: 27405244 18. Segal L, Morelle D, Kaaber K, Destexhe E, Garcon N. Non-clinical safety assessment of single and repeated intramuscular administration of a human papillomavirus-16/18 vaccine in rabbits and rats. Journal of applied toxicology: JAT. 2015; 35(12):1577–85. doi: 10.1002/jat.3131 PMID: 25752809 19. Pujol JL, Vansteenkiste JF, De Pas TM, Atanackovic D, Reck M, Thomeer M, et al. Safety and Immuno￾genicity of MAGE-A3 Cancer Immunotherapeutic with or without Adjuvant Chemotherapy in Patients with Resected Stage IB to III MAGE-A3-Positive Non-Small-Cell Lung Cancer. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer. 2015; 10 (10):1458–67. 20. Minhinnick A, Satti I, Harris S, Wilkie M, Sheehan S, Stockdale L, et al. A first-in-human phase 1 trial to evaluate the safety and immunogenicity of the candidate tuberculosis vaccine MVA85A-IMX313, administered to BCG-vaccinated adults. Vaccine. 2016; 34(11):1412–21. doi: 10.1016/j.vaccine.2016. 01.062 PMID: 26854906 21. Belafsky PC, Peake J, Smiley-Jewell SM, Verma SP, Dworkin-Valenti J, Pinkerton KE. Soot and house dust mite allergen cause eosinophilic laryngitis in an animal model. The Laryngoscope. 2016; 126 (1):108–12. doi: 10.1002/lary.25467 PMID: 26197967 22. Kimber I, Dearman RJ, Basketter DA, Boverhof DR. Chemical respiratory allergy: reverse engineering an adverse outcome pathway. Toxicology. 2014; 318:32–9. doi: 10.1016/j.tox.2014.02.001 PMID: 24534103 23. Ghatan PH, Marcusson-Stahl M, Matura M, Bjorkheden C, Lundborg P, Cederbrant K. Sensitization to omeprazole in the occupational setting. Contact dermatitis. 2014; 71(6):371–5. doi: 10.1111/cod.12305 PMID: 25310916 24. Zhai SQ, Yu N, Guo WW, Zhang Y. Effect of Binghuang ear drop treatment on otitis externa in guinea pigs. Cell biochemistry and biophysics. 2014; 70(3):1813–5. doi: 10.1007/s12013-014-0134-y PMID: 25269771 25. Persson GR, Engel LD, Whitney CW, Weinberg A, Moncla BJ, Darveau RP, et al. Macaca fascicularis as a model in which to assess the safety and efficacy of a vaccine for periodontitis. Oral microbiology and immunology. 1994; 9(2):104–11. PMID: 8008428 26. Leroux-Roels G, Marchant A, Levy J, Van Damme P, Schwarz TF, Horsmans Y, et al. Impact of adju￾vants on CD4+ T cell and B cell responses to a protein antigen vaccine: Results from a phase II, ran￾domized, multicenter trial. Clinical immunology. 2016; 169:16–27. doi: 10.1016/j.clim.2016.05.007 PMID: 27236001 A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) PLOS ONE | DOI:10.1371/journal.pone.0170313 January 19, 2017 11 / 11