Article
Author: Zheng, Feng-Xian ; Li, Yi-Min ; Guo, Dong-Ping ; Wang, Jun-Zhi ; Hu, Yue-Mei ; Zhang, Jun ; Zhao, Hui ; Li, Cai-Hong ; Zhu, Feng-Cai ; Chen, Wen ; Su, Ying-Ying ; Li, Yan-Ping ; Pan, Hui-Rong ; Zhao, Jun ; Zhao, Chao ; Li, Juan ; Zhang, Wen-Hua ; Ke, Li-Dong ; Zhao, Bin ; Tang, Jie ; Wu, Ting ; Lin, Zhi-Jie ; Gao, Guo-Qi ; Guo, Meng ; Li, Rong-Cheng ; Li, Shao-Wei ; Li, Qing ; Hong, Ying ; Li, Mei ; Xia, Ning-Shao ; Pan, Qin-Jing ; Liu, Wen-Yu ; Wu, Xin ; Jiang, Yun-Fei ; Dai, Cui-Hong ; Qiao, You-Lin ; Cui, Xue-Lian ; Li, Chang-Gui ; Chu, Kai ; Zhao, Fang-Hui ; Wei, Li-Hui ; Li, Ba-Yi ; Li, Ming-Qiang ; Huang, Shou-Jie ; Zhang, Xun
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 were induced and persisted for at least 42 months.
Conclusions:The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18–associated high-grade genital lesions and persistent infection in women.