Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial

作者：You‐Lin Qiao, Ting Wu, Rongcheng Li, Yuemei Hu, Lihui Wei, Changgui Li, Wen Chen, Shoujie Huang, Fanghui Zhao, Mingqiang Li, Qinjing Pan, Xun Zhang, Li Q, Ying Hong, Chao Zhao, Wenhua Zhang, Yanping Li, Kai Chu, Mei Li, Yunfei Jiang, Juan Li, Hui Zhao, Zhijie Lin, Xuelian Cui, Wen Yu, Caihong Li, Dongping Guo, Li-Dong Ke, Xin Wu, Jie Tang, Guo-Qi Gao, Ba-Yi Li, Bin Zhao, Fengxian Zheng, Cui-Hong Dai, Meng Guo, Jun Zhao, Yingying Su, Junzhi Wang, Fengcai Zhu, Shaowei Li, Huirong Pan, Yimin Li, Jun Zhang, Ningshao Xia · 发表于：JNCI Journal of the National Cancer Institute · 年份：2019 · DOI：10.1093/jnci/djz074 · 被引用次数：180 · 研究领域：Cervical Cancer and HPV Research、Immunotherapy and Immune Responses、Reproductive tract infections research

BACKGROUND: The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. METHODS: A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. RESULTS: In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types...