All authors had access to the statistical analysis statement and contributed to interpretation of the results. (BioNet, Bangkok, Thailand) has developed a new recombinant strain expressing a genetically-detoxified PT (PTgen)18 which retains the functional antigenic properties of native PT but without its toxicity.17,18,19 Here, we report the results of the first clinical trial designed to evaluate the safety and immunogenicity of BioNet’s aP vaccine alone or combined with tetanus and diphtheria toxoids (TdaP) in healthy adults. Results Study subjects and demographic characteristics A total of 67 subjects were screened, of whom 60 were enrolled, vaccinated and included in the security analysis (Fig.?1). Four subjects were excluded from your immunogenicity analysis: 3 subjects at Day 7 after vaccination (2 for incorrect labeling of the serum samples, one for missed visit) and one subject at Day 28 after vaccination for having received tetanus vaccine due to a squirrel bite during the study. Demographic and baseline characteristics of study subjects were comparable among the 3 vaccine groups (Table?1). Open in a separate window Physique 1. Subjects Disposition. Table 1. Summary SC-26196 of demographics FLJ23184 at baseline by vaccine group. 0.05). One subject reported severe induration which resolved in a few days without sequelae. The systemic post-immunization reactions were similar in all vaccine groups, most of which were moderate in severity. The most frequently reported systemic post-immunization reaction was myalgia (10C35%), followed SC-26196 by fatigue (10C25%) and malaise (5C25%) ( Table?2). Mild fever was reported by one subject in the Adacel? group. All post-immunization reactions were transient and resolved without sequelae. Table 2. Local and systemic reactions during 7?d after vaccination by vaccine group. = 0.001, Table?3A). SC-26196 One month after vaccination, seroresponse rates to PT, FHA and PRN ranged from 78% to 100% in all vaccine groups (Table?3A), with SC-26196 no statistically significant difference. Table 3A. Seroresponse rates as defined by the percentage of subjects with 4-fold increase as compared to baseline values of anti-PT IgG, anti-FHA IgG, anti-PRN IgG and anti-PT neutralizing antibody titers at 7 and 28?d after vaccination. 0.01) in BioNet’s aP and TdaP than in the Adacel? group (Table?3B). At Day 28, anti-PT and anti-FHA IgG GMTs were significantly higher in BioNet’s aP and TdaP vaccine groups [anti-PT antibody: 264.0 IU/mL (95% CI, 113.70C612.92) and 268.5 IU/mL (95% CI, 162.20C444.39), respectively; anti-FHA: 728.0 IU/mL (95% CI, 545.94C970.66) and 666.1 IU/mL (95% CI, 498.61C889.79), respectively] compared to Adacel? group [anti-PT: 50.79 IU/mL (95% CI, 36.98C69.75); anti-FHA: 159.6 IU/mL (95% CI, 114.49C222.49)] (Table?3B). Day 28 anti-PRN IgG GMTs were higher in Adacel? than BioNet’s aP and BioNet’s TdaP vaccinees (Table?3B), even though difference was not statistically significant. At baseline, all subjects in BioNet’s TdaP vaccine and Adacel? groups experienced seroprotective level (0.1 IU/mL) of anti-tetanus and anti-diphtheria IgG antibodies. At 7?d after Adacel? immunization, subjects experienced significantly higher ( SC-26196 0.05) anti-diphtheria antibody titers [0.72 IU/mL (95% CI, 0.46C1.12)] than those in BioNet’s TdaP vaccine group [0.39 IU/mL (95% CI, 0.24C0.62)]. There was no statistically significant difference in the anti-tetanus and anti-diphtheria GMTs at 28?d after vaccination in both BioNet’s TdaP vaccine and Adacel? groups [7.22 IU/mL (95% CI, 5.35C9.76) and 7.66 IU/mL (95% CI, 6.53C8.98), respectively for anti-tetanus antibody and 0.53 IU/mL (95% CI, 0.31C0.90) and 0.88 IU/mL (95% CI, 0.59C1.32), respectively for anti-diphtheria antibody]. PT neutralizing assay At 7 and 28?d after vaccination, the seroresponse rates to anti-PT neutralizing titers were similar in all 3 vaccines groups with no statistically significant difference (Table?3A). At 28?d post-immunization, the GMTs of anti-PT neutralizing antibody (Nab) in BioNet’s aP [151.5 IU/mL (95% CI, 54.48C421.33)] and TdaP [149.5 IU/mL (95% CI, 81.62C273.74)] vaccinees were significantly higher than in Adacel? group [33.40 IU/mL (95% CI, 21.22C52.58)] ( 0.01). Proportion of subjects with ELISA anti-PT IgG and anti-PT Nab above cut-off antibody levels The proportion of subjects with ELISA anti-PT IgG antibody cut-off titers between 20 and 120 IU/mL is usually shown in Fig.?2. At 28?d post-immunization, more than 80% of subjects in BioNet’s aP and BioNet’s TdaP vaccine groups had anti-PT IgG titer above 80 IU/mL compared to approximately 20% of subjects in the Adacel? group (Fig.?2). Open in a separate window Physique 2. Percentages of subjects with cut-off value titers of ELISA and Nab anti-PT at baseline and 28?d after vaccination. The distribution of anti-PT Nab titers was comparable, with approximately 70% of subjects in BioNet’s aP and TdaP vaccine groups with anti-PT Nab titer 80 IU/mL vs approximately 20% of subjects in the Adacel? group (Fig.?2). Conversation This first-in-human study indicated a similar reactogenicity and security profile of BioNet’s PTgen-containing vaccines and Adacel?, except for a few more transient local reactions following BioNet’s TdaP immunization. It is unlikely that these reactions were due to recent exposure to Tetanus or Diphtheria vaccines as potential volunteers were excluded during screening visit if they experienced received Tetanus or Diphtheria.