The safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine among patients undergoing elective surgery for closed fractures: A randomized,double-blind,placebo-controlled,multicenter phase 2 clinical trial |
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| Institution: | 1. Department of Trauma and Orthopedics, Beijing Jishuitan Hospital, Beijing, China;2. 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;3. Trauma Emergency Center of Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;4. Orthopedic Department of Southwest Hospital, Army Medical University, Chongqing, China;5. Orthopedic Department of the Eighth Affiliated Hospital, Sun Yat-sen University, Zhongshan, Guangdong, China;6. Orthopedic Department of West China Hospital of Sichuan University, Chengdu, Sichuan, China;7. Chinese Osteo-traumatology Department of Shenyang Orthopedic Hospital, Shenyang, Liaoning, China;8. Department of Trauma and Orthopedics of the 2nd School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China;9. Orthopedic Department of Liaocheng People''s Hospital, Liaocheng, Shandong, China;10. Orthopedic Department of Shanxi Provincial People''s Hospital, Taiyuan, Shanxi, China;11. Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China;12. Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China;13. State Key Laboratory of Pharmaceutical Biotechnology, Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China;14. Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation, Nanjing, Jiangsu, China;15. National Engineering Research Center of Immunological, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China;p. Chengdu Olymvax Biopharmaceuticals Inc., Chengdu, Sichuan, China;q. State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, China;1. College of Medicine, University of Florida, Gainesville, FL, USA;2. Department of Orthopaedic Surgery and Sports Medicine, University of Florida, Gainesville, FL, USA;1. Dept. of Medical Life Science, Kyushu University of Health and Welfare, Nobeoka, Miyazaki, Japan;2. Institute of Immunology, Junsei Educational Institute, Nobeoka, Miyazaki, Japan;3. Department of Academic Research Support Promotion Facility, Center for Research Promotion and Support, Fujita Health University, Aichi, Japan;4. MabGenesis KK, Nagoya, Japan;5. Medicine and Immunology, University of Toronto, Ontario, Canada;6. The Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India;7. Centre for Advancing Clinical Research (CACR), University of Yamanashi – School of Medicine, Chuo, Japan;8. The Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India;9. Antony- Xavier Interdisciplinary Scholastics (AXIS), GN Corporation Co. Ltd., Kofu, Japan;1. Vaxine Pty Ltd, Bedford Park, Adelaide, SA 5042, Australia;2. Flinders University, Bedford Park, Adelaide, SA 5042, Australia;3. Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, UT 84322, USA;1. AMGA, One Prince Street, Alexandria, VA 22314, USA;2. Nice Healthcare, Minneapolis, MN, USA;1. The Biosecurity Program, Kirby Institute, Faculty of Medicine and Health Sciences, University of New South Wales, New South Wales, Australia;2. College of Health Solutions and Watts College of Public Service and Community Services, Arizona State University, United States;3. The School of Population Health, Faculty of Medicine and Health Sciences, University of New South Wales, New South Wales, Australia |
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| Abstract: | BackgroundVaccines 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.MethodsA 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.ResultsA 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.ConclusionsrFSAV 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. |
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| Keywords: | Vaccine Safety Immunogenicity Efficacy Closed fractures |
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