Infant Botulism Treatment and Prevention Program, Infectious Diseases Laboratory Branch, Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond, CA 94804, USA.
Infant Botulism Treatment and Prevention Program, Infectious Diseases Laboratory Branch, Division of Communicable Disease Control, Center for Infectious Diseases, California Department of Public Health, Richmond, CA 94804, USA.
Vaccine. 2018 Apr 5;36(15):2041-2048. doi: 10.1016/j.vaccine.2018.02.042. Epub 2018 Feb 21.
We undertook an open-label, uncontrolled study of investigational recombinant botulinum vaccine for botulinum neurotoxin (BoNT) serotypes A and B (rBV A/B) to assess its safety and immunogenicity in healthy volunteers who had been previously immunized with investigational pentavalent botulinum toxoid. Study participants who wished to do so could donate their hyperimmune plasma for production of Human Botulism Immune Globulin Intravenous (BIG-IV, BabyBIG®).
A single 0.5 ml (mL), 40-microgram intramuscular injection of rBV A/B was administered to study participants. Post-vaccination sera collected at approximately 2-week intervals were evaluated for anti-BoNT/A and anti-BoNT/B neutralizing antibody concentrations (NAC). Local and systemic treatment-emergent adverse events (TEAEs) were identified by clinical and laboratory monitoring for 12 weeks post-vaccination with a final telephone follow-up for additional safety assessment at 6 months. The primary endpoint for immunogenicity was a ≥4-fold rise in NAC in ≥50% of participants by Week 4 post-vaccination.
All 45 enrolled participants completed the study. Forty-two of 45 participants (93.3%) experienced at least one TEAE. Overall, 138 of 218 (63.3%) reported TEAEs were treatment-related, the majority of which were mild injection-site reactions. No serious or unexpected adverse events occurred. The study achieved its primary immunogenicity endpoint with 37/45 (82.2%) participants and 39/45 (86.7%) participants having a ≥4-fold rise in NAC to anti-BoNT/A and to anti-BoNT/B, respectively, by Week 4 post-vaccination.
A single 0.5 mL dose of rBV A/B was safe, well-tolerated and immunogenic in participants previously immunized with pentavalent botulinum toxoid. The tolerability and immunogenicity characteristics of rBV A/B vaccination of individuals with existing BoNT immunity support its potential future use to provide occupational protection to botulism laboratory workers. Almost all study participants donated hyperimmune plasma for production of BIG-IV. ClinicalTrials.gov registration number: NCT01701999.
我们进行了一项开放性、非对照研究，评估先前已接种过研究用五价肉毒毒素的健康志愿者使用研究用重组肉毒梭菌神经毒素（BoNT）A 型和 B 型疫苗（rBV A/B）的安全性和免疫原性。希望这样做的研究参与者可以捐献他们的高免疫血浆，用于生产人破伤风免疫球蛋白静脉注射剂（BIG-IV，BabyBIG®）。
研究参与者接受单次 0.5 毫升（ml）、40 微克的 rBV A/B 肌肉内注射。大约每隔 2 周采集一次接种后血清，评估其抗 BoNT/A 和抗 BoNT/B 中和抗体浓度（NAC）。接种后 12 周通过临床和实验室监测识别局部和全身治疗后出现的不良事件（TEAEs），并在 6 个月时进行最终电话随访以进行额外的安全性评估。免疫原性的主要终点是接种后第 4 周时 NAC 至少增加 4 倍的参与者比例≥50%。
所有 45 名入组的参与者均完成了研究。45 名参与者中有 42 名（93.3%）至少经历过一次 TEAEs。总体而言，218 例 TEAEs 中有 138 例（63.3%）与治疗相关，其中大多数为轻度注射部位反应。未发生严重或意外的不良事件。该研究达到了主要的免疫原性终点，接种后第 4 周时，45 名参与者中有 37 名（82.2%）和 39 名（86.7%）的 NAC 对 BoNT/A 和 BoNT/B 的增加均≥4 倍。
先前已接种过五价肉毒毒素的参与者接受单次 0.5ml 剂量的 rBV A/B 是安全的，耐受良好且具有免疫原性。rBV A/B 接种在具有现有 BoNT 免疫的个体中的耐受性和免疫原性特征支持其未来潜在用途，以提供对肉毒梭菌实验室工作者的职业保护。几乎所有研究参与者都捐献了高免疫血浆，用于生产 BIG-IV。临床试验注册编号：NCT01701999。
