Department of Trauma and Orthopedics, Beijing Jishuitan Hospital, Beijing, China.
DTaP and Toxins Division, National Institutes for Food and Drug Control, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, Beijing, China.
Vaccine. 2023 Aug 31;41(38):5562-5571. doi: 10.1016/j.vaccine.2023.07.047. Epub 2023 Jul 27.
Vaccines are urgently required to control Staphylococcus aureus hospital and community infections and reduce the use of antibiotics. Here, we report the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in patients undergoing elective surgery for closed fractures.
A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial was carried out in 10 clinical research centers in China. Patients undergoing elective surgery for closed fractures, aged 18-70 years, were randomly allocated at a ratio of 1:1 to receive the rFSAV or placebo at a regimen of two doses on day 0 and another dose on day 7. All participants and investigators remained blinded during the study period. The safety endpoint was the incidence of adverse events within 180 days. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as opsonophagocytic antibodies.
A total of 348 eligible participants were randomized to the rFSAV (n = 174) and placebo (n = 174) groups. No grade 3 local adverse events occurred. There was no significant difference in the incidence of overall systemic adverse events between the experimental (40.24 %) and control groups (33.72 %) within 180 days after the first immunization. The antigen-specific binding antibodies started to increase at days 7 and reached their peaks at 10-14 days after the first immunization. The rapid and potent opsonophagocytic antibodies were also substantially above the background levels.
rFSAV is safe and well-tolerated in patients undergoing elective surgery for closed fractures. It elicited rapid and robust specific humoral immune responses using the perioperative immunization procedure. These results provide evidence for further clinical trials to confirm the vaccine efficacy. China's Drug Clinical Trials Registration and Information Publicity Platform registration number: CTR20181788. WHO International Clinical Trial Registry Platform identifier: ChiCTR2200066259.
急需疫苗来控制金黄色葡萄球菌医院和社区感染，并减少抗生素的使用。在这里，我们报告了一种重组五抗原金黄色葡萄球菌疫苗（rFSAV）在择期接受闭合性骨折手术的患者中的安全性和免疫原性。
在中国的 10 个临床研究中心进行了一项随机、双盲、安慰剂对照、多中心的 2 期临床试验。年龄在 18-70 岁之间，择期接受闭合性骨折手术的患者，按照 1:1 的比例随机分配，在第 0 天和第 7 天接受 rFSAV 或安慰剂两剂，第 7 天接受一剂。在研究期间，所有参与者和研究者均保持盲法。安全性终点是 180 天内不良事件的发生率。免疫原性终点包括接种后五种抗原的特异性抗体水平以及调理吞噬抗体。
共有 348 名符合条件的患者被随机分配到 rFSAV（n=174）和安慰剂（n=174）组。没有发生 3 级局部不良事件。首次免疫后 180 天内，实验组（40.24%）和对照组（33.72%）总体全身不良事件发生率无显著差异。抗原特异性结合抗体在第 7 天开始增加，在首次免疫后 10-14 天达到峰值。快速而有效的调理吞噬抗体也明显高于背景水平。
rFSAV 用于择期接受闭合性骨折手术的患者是安全且耐受良好的。它采用围手术期免疫程序，快速产生强大的特异性体液免疫反应。这些结果为进一步的临床试验提供了证据，以确认疫苗的疗效。中国药物临床试验注册和信息公示平台注册号： CTR20181788。世界卫生组织国际临床试验注册平台标识： ChiCTR2200066259。
