圆PLoS|oNE A Pre-Clinical Safety Evaluation of SBP(HBsAg-Binding Protein) Table 2. GLP allergic reaction test in guinea pig Group Positive rate Extent of reaction Negative control Positive control ~十十十 s(05m) 044 Hs(0.5m) ~十十十 negative allergy: + weakly positive allergy, ++ positive allergy, +++ strong positive allergy, ++++ do:10.1371/ ournal pone017031302 days afterwards(Fig 4). For SBP-adjuvanted vaccine groups, the lower dosage appeared to induce higher antibody production according to our results. It seems that the SBP-specific ntibody was produced, and then levels declined in a dosage - independent manner. The detailed mechanism is not yet clear. SBP-adjuvanted HBV vaccine could induce stronger immune response in Macaca fascicularis than unadjuvanted vaccine, without any side Macaca fascicularis were used to determine the effects of SBP-adjuvanted vaccine in primates As shown in Fig 5, animals that received SBP-adjuvanted vaccine had higher antibody levels after day 30 than the animals that received non-adjuvanted vaccine. This suggests that SBP nt to the hpv 1.5 S(0.5m) S(1.5m) 1.0 Hs(0.5m) HS(1.5m) 0.5 0.0 0d7d14d21d28d42d72d cific antibody production in rats. Rats (n= 10)were immunized intramuscularly 3 times at a 2-week interval with vacci ether with SBP (H-S). Blood samples were collected on indicated time points and anti-SBP total lgG was measured by 101371/ ournal pone.0170313 PLOS ONE DO1: 10. 1371/journal pone. 0170313 January 19, 2017days afterwards (Fig 4). For SBP-adjuvanted vaccine groups, the lower dosage appeared to induce higher antibody production according to our results. It seems that the SBP-specific antibody was produced, and then levels declined in a dosage-independent manner. The detailed mechanism is not yet clear. SBP-adjuvanted HBV vaccine could induce stronger immune response in Macaca fascicularis than unadjuvanted vaccine, without any side effects Macaca fascicularis were used to determine the effects of SBP-adjuvanted vaccine in primates. As shown in Fig 5, animals that received SBP-adjuvanted vaccine had higher antibody levels after day 30 than the animals that received non-adjuvanted vaccine. This suggests that SBP could be a good adjuvant to the HPV vaccine. Table 2. GLP allergic reaction test in guinea pig. Group Positive rate Extent of reaction Negative control 0 - Positive control 1 +~+++ S (0.5ml) 0.44 +~++ S (1.5ml) 1 +~++++ H-S (0.5ml) 0 - H-S (1.5ml) 0.67 +~+++ –, negative allergy; +, weakly positive allergy; ++, positive allergy; +++, strong positive allergy; ++++, extremely positive allergy. doi:10.1371/journal.pone.0170313.t002 Fig 4. SBP-specific antibody production in rats. Rats (n = 10) were immunized intramuscularly 3 times at a 2-week interval with vaccine alone (H) or together with SBP (H-S). Blood samples were collected on indicated time points and anti-SBP total IgG was measured by ELISA. Results are expressed as the means ± SEM. * p<0.05. doi:10.1371/journal.pone.0170313.g004 A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) PLOS ONE | DOI:10.1371/journal.pone.0170313 January 19, 2017 7 / 11