圆PLoS|oNE A Pre-Clinical Safety Evaluation of SBP(HBsAg-Binding Protein) Project administration: NZ JX. Resources: CS BL Validation: BL JW Writing-original draft: JW Writing- review editing: JW IK. References 1. Wei MJ, Pan XN, Wei KP, Li XH, Liu XL, Zhang XM, et al. Efficacy of HBV-pulsed DCs in combination with entecavir in patients with chronic hepatitis B infection. International immunopharmacology 2015: 27(2)23843.do:10.1016/ . intim201506019PMD:26118632 2. Hall S, Desbrow B, Anoopkumar-Dukie S, Davey AK, Arora D, McDermott C, et al. A review of the bio- activity of coffee, caffeine and key coffee constituents on inflammatory responses linked to depression Food Research International. 2015: 76: 626-36. 3. Janssen JM, Jackson S, Heyward WL, Janssen RS Immunogenicity of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant(HBsAg-1018)compared with a licensed hepatitis B vaccine in subpopulations of healthy adults 18-70 years of age. Vaccine. 2015: 33(31): 3614-8. doi: 10 1016/ vaccine201505070PMD:26067185 duction of a robust T- n-andlow-responders to conventional vaccination against hepatitis B byusir third generation PreS/S vaccine. Vaccine. 2014: 32: 5077-5082. doi: 10.1016/ vaccine. 2014.06.076 PMID:24975813 5. LiX, Thakkar SG, Ruwona TB, Williams RO 3rd, Cui Z. A method of lyophilizing vaccines containing aluminum salts into a dry powder without causing particle aggregation or decreasing the immunogenic ity following reconstitution Joumal of controlled release: official journal of the Controlled Release Soci- ety.2015;204385 6. Nakaya HI, Clutterbuck E, Kazmin D, Wang L, Cortese M, Bosinger SE, et aL. Systems biology of immu Proceedings of the National Academy of Sciences of the United States of America. 2016: 113(7): 1853- 8.doi:101073pnas1519690113PMD:26755593 7. Yam KK, Gupta J Allen EK, Burt KR, Beaulieu E, Mallett CP, et al. Comparison of As03 and Alum n immune responses elicited by AH3N2 split influenza vaccine in young, mature and aged BALB/c mi Vaccine.2016:34(12):14451.doi:10.1016/ vaccine201602012PMD:26873056 8. Didierlaurent AM, Morel S, Lockman L, Giannini SL, Bisteau M, carlsen H, et al. aso4, an aluminum salt-and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity Journal of immunology. 2009: 183(10): 6186-97. journa.2015:8(1):7.doi:10.1186/s4041301500605PMD:25780491 10. Zhang C, Gong L, Chen Y, Wang X, Zhu S, LiD, et al. A human-derived protein SBP(HBsAg- binding protein)can bind to hepatitis B virus surface antigen(HBsAg) and enhance the immune response to vaccine. Molecular Immunology 2013: 53 (1-2): 60-71. doi: 10. 1016/. molimm. 201206014PMID:22809814 11. Segal L, Wouters S, Morelle D, Gautier G, Le Gal J, Martin T, et al. Non-clinical safety and biodistribu- on of As03-adjuvanted inactivated pandemic influenza vaccines. Joumal of applied toxicology: JAT. 2015:35(12:1564-76.doi:10.1002/at3130PMD:25727696 nary safety an Y, TsukuiT, Ishii KJ, Coban C Current status of synthetic hemozoin adjuvant: A prelimi- ty evaluation Vaccine 2016: 34(18): 2055-61. doi: 10. 1016/ vaccine. 2016.02.064 PMID 13.:860Paem PLOS ONE DO1: 10. 1371/journal pone. 0170313 JanuaryProject administration: NZ JX. Resources: CS BL. Software: JW. Supervision: NZ. Validation: BL JW. Visualization: JW. Writing – original draft: JW. Writing – review & editing: JW IK. References 1. Wei MJ, Pan XN, Wei KP, Li XH, Liu XL, Zhang XM, et al. Efficacy of HBV-pulsed DCs in combination with entecavir in patients with chronic hepatitis B infection. International immunopharmacology. 2015; 27(2):238–43. doi: 10.1016/j.intimp.2015.06.019 PMID: 26118632 2. Hall S, Desbrow B, Anoopkumar-Dukie S, Davey AK, Arora D, McDermott C, et al. A review of the bio￾activity of coffee, caffeine and key coffee constituents on inflammatory responses linked to depression. Food Research International. 2015; 76:626–36. 3. Janssen JM, Jackson S, Heyward WL, Janssen RS. Immunogenicity of an investigational hepatitis B vaccine with a toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in subpopulations of healthy adults 18–70 years of age. Vaccine. 2015; 33(31):3614–8. doi: 10. 1016/j.vaccine.2015.05.070 PMID: 26067185 4. Krawczyk Adalbert, Ludwig Charlotte, Jochum Christoph et al. Induction of a robust T- and B-cell immune response in non- andlow-responders to conventional vaccination against hepatitis B byusing a third generation PreS/S vaccine. Vaccine. 2014; 32:5077–5082. doi: 10.1016/j.vaccine.2014.06.076 PMID: 24975813 5. Li X, Thakkar SG, Ruwona TB, Williams RO 3rd, Cui Z. A method of lyophilizing vaccines containing aluminum salts into a dry powder without causing particle aggregation or decreasing the immunogenic￾ity following reconstitution. Journal of controlled release: official journal of the Controlled Release Soci￾ety. 2015; 204:38–50. 6. Nakaya HI, Clutterbuck E, Kazmin D, Wang L, Cortese M, Bosinger SE, et al. Systems biology of immu￾nity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood. Proceedings of the National Academy of Sciences of the United States of America. 2016; 113(7):1853– 8. doi: 10.1073/pnas.1519690113 PMID: 26755593 7. Yam KK, Gupta J, Allen EK, Burt KR, Beaulieu E, Mallett CP, et al. Comparison of AS03 and Alum on immune responses elicited by A/H3N2 split influenza vaccine in young, mature and aged BALB/c mice. Vaccine. 2016; 34(12):1444–51. doi: 10.1016/j.vaccine.2016.02.012 PMID: 26873056 8. Didierlaurent AM, Morel S, Lockman L, Giannini SL, Bisteau M, Carlsen H, et al. AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. Journal of immunology. 2009; 183(10):6186–97. 9. Jensen-Jarolim E. Aluminium in Allergies and Allergen immunotherapy. The World Allergy Organization journal. 2015; 8(1):7. doi: 10.1186/s40413-015-0060-5 PMID: 25780491 10. Zhang C, Gong L, Chen Y, Wang X, Zhu S, Li D, et al. A human-derived protein SBP (HBsAg-binding protein) can bind to hepatitis B virus surface antigen (HBsAg) and enhance the immune response to hepatitis B virus (HBV) vaccine. Molecular Immunology. 2013; 53(1–2):60–71. doi: 10.1016/j.molimm. 2012.06.014 PMID: 22809814 11. Segal L, Wouters S, Morelle D, Gautier G, Le Gal J, Martin T, et al. Non-clinical safety and biodistribu￾tion of AS03-adjuvanted inactivated pandemic influenza vaccines. Journal of applied toxicology: JAT. 2015; 35(12):1564–76. doi: 10.1002/jat.3130 PMID: 25727696 12. Lee MS, Igari Y, Tsukui T, Ishii KJ, Coban C. Current status of synthetic hemozoin adjuvant: A prelimi￾nary safety evaluation. Vaccine. 2016; 34(18):2055–61. doi: 10.1016/j.vaccine.2016.02.064 PMID: 26976665 13. Block TM, Rawat S, Brosgart CL. Chronic hepatitis B: A wave of new therapies on the horizon. Antiviral research. 2015; 121:69–81. doi: 10.1016/j.antiviral.2015.06.014 PMID: 26112647 A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) PLOS ONE | DOI:10.1371/journal.pone.0170313 January 19, 2017 10 / 11