Langley Joanne M, Aggarwal Naresh, Toma Azhar, Halperin Scott A, McNeil Shelly A, Fissette Laurence, Dewé Walthere, Leyssen Maarten, Toussaint Jean-François, Dieussaert Ilse
Canadian Center for Vaccinology, IWK Health Centre-Nova Scotia Health Authority-Dalhousie University, Halifax.
Aggarwal and Associates Limited, Brampton.
J Infect Dis. 2017 Jan 1;215(1):24-33. doi: 10.1093/infdis/jiw453. Epub 2016 Sep 29.
Respiratory syncytial virus (RSV) is a leading cause of childhood bronchiolitis and pneumonia, particularly in early infancy. Immunization of pregnant women could boost preexisting immune responses, providing passive protection to newborns through placental transfer of anti-RSV antibody.
In this first-in-humans clinical trial of a purified recombinant RSV protein F vaccine engineered to preferentially maintain prefusion conformation (RSV-PreF), 128 healthy men 18-44 years old were randomized to one dose of a RSV-PreF vaccine containing 10, 30, or 60 µg of RSV-PreF antigen, with or without alum adjuvant, or control, and followed for one year for safety and immunogenicity outcomes.
Injection site pain was the most common adverse event, reported by up to 81.3% of participants. The highest RSV neutralizing antibody responses were in the 30 µg RSV-PreF/alum, 60 µg RSV-PreF/alum, and 60 µg RSV-PreF/nonadjuvant groups. Responses were evident on day 7, and 30 days after vaccination these participants had RSV-A neutralizing antibody titers of ≥1:512, and >70% had titers of 1:1024, with titers increasing by 3.2-4.9 fold. Responses remained high on day 60 but waned on days 180 and 360.
The RSV-PreF vaccine elicited rapid RSV neutralizing antibody responses in healthy young men, with an acceptable adverse event profile.
呼吸道合胞病毒（RSV）是儿童细支气管炎和肺炎的主要病因，尤其是在婴儿早期。孕妇免疫可增强预先存在的免疫反应，通过胎盘传递抗RSV抗体为新生儿提供被动保护。
在这项针对一种经工程改造以优先保持预融合构象的纯化重组RSV蛋白F疫苗（RSV-PreF）的首例人体临床试验中，128名18至44岁的健康男性被随机分为接受一剂含10、30或60μg RSV-PreF抗原的RSV-PreF疫苗，加或不加明矾佐剂，或作为对照，并随访一年以观察安全性和免疫原性结果。
注射部位疼痛是最常见的不良事件，高达81.3%的参与者报告有此症状。最高的RSV中和抗体反应出现在30μg RSV-PreF/明矾、60μg RSV-PreF/明矾和60μg RSV-PreF/无佐剂组。在第7天就有明显反应，接种疫苗30天后，这些参与者的RSV-A中和抗体滴度≥1:512，超过70%的人滴度为1:1024，滴度增加了3.2至4.9倍。在第60天反应仍然很高，但在第180天和360天有所下降。
RSV-PreF疫苗在健康年轻男性中引发了快速的RSV中和抗体反应，且不良事件情况可接受。
