Efficacy, safety, and immunogenicity of an Escherichia coli-produced Human Papillomavirus (16 and 18) L1 virus-like-particle vaccine: end-of-study analysis of a phase 3, double-blind, randomised, controlled trial,The Lancet Infectious Diseases

当前位置： X-MOL 学术 › Lancet Infect Dis › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Efficacy, safety, and immunogenicity of an Escherichia coli-produced Human Papillomavirus (16 and 18) L1 virus-like-particle vaccine: end-of-study analysis of a phase 3, double-blind, randomised, controlled trial
The Lancet Infectious Diseases ( IF 36.4 ) Pub Date : 2022-08-26 , DOI: 10.1016/s1473-3099(22)00435-2
Fang-Hui Zhao ₁ , Ting Wu ₂ , Yue-Mei Hu ₃ , Li-Hui Wei ₄ , Ming-Qiang Li ₅ , Wei-Jin Huang ₆ , Wen Chen ₁ , Shou-Jie Huang ₂ , Qin-Jing Pan ₁ , Xun Zhang ₁ , Ying Hong ₇ , Chao Zhao ₄ , Qing Li ₈ , Kai Chu ₃ , Yun-Fei Jiang ₇ , Ming-Zhu Li ₄ , Jie Tang ₉ , Cai-Hong Li ₁₀ , Dong-Ping Guo ₁₁ , Li-Dong Ke ₁₂ , Xin Wu ₅ , Xing-Mei Yao ₁₃ , Jian-Hui Nie ₆ , Bi-Zhen Lin ₁₄ , Yu-Qian Zhao ₁ , Meng Guo ₁₃ , Jun Zhao ₁₃ , Feng-Zhu Zheng ₁₄ , Xiao-Qian Xu ₁ , Ying-Ying Su ₂ , Qiu-Fen Zhang ₁₄ , Guang Sun ₁₄ , Feng-Cai Zhu ₃ , Shao-Wei Li ₂ , Yi-Min Li ₁₅ , Hui-Rong Pan ₁₄ , Jun Zhang ₂ , You-Lin Qiao ₁₆ , Ning-Shao Xia ₁₇

Affiliation

National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen, Fujian, China; Xiang An Biomedicine Laboratory, Xiamen, Fujian, China.
Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China.
Peking University People's Hospital, Beijing, China.
Liuzhou Center for Disease Control and Prevention, Liuzhou, Guangxi, China.
National Institute for Food and Drug Control, Beijing, China.
the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, Guangdong, China.
Funing Center for Disease Control and Prevention, Funing, Jiangsu, China.
Xinmi Maternal and Child Health Hospital, Xinmi, Henan, China.
Yangcheng Maternal and Child Health Hospital, Yangcheng, Shanxi, China.
Fengning Hospital of Traditional Chinese Medicine, Fengning, Hebei, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen, Fujian, China.
Xiamen Innovax Biotech Xiamen, Fujian, China.
Beijing Wantai Biological Pharmacy Enterprise, Beijing, China.
School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Collaborative Innovation Center of Biologic Products, School of Public Health, Xiamen University, Xiamen, Fujian, China; Xiang An Biomedicine Laboratory, Xiamen, Fujian, China; Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences, China.

Background

This Escherichia coli-produced bivalent HPV 16 and 18 vaccine was well tolerated and effective against HPV 16 and 18 associated high-grade genital lesions and persistent infection in interim analysis of this phase 3 trial. We now report data on long-term efficacy and safety after 66 months of follow-up.

Methods

This phase 3, double-blind, randomised, controlled trial was done in five study sites in China. Eligible participants were women aged 18–45 years, with intact cervix and 1–4 lifetime sexual partners. Women who were pregnant or breastfeeding, had chronic disease or immunodeficiency, or had HPV vaccination history were excluded. Women were stratified by age (18–26 and 27–45 years) and randomly (1:1) allocated by software (block randomisation with 12 codes to a block) to receive three doses of the E coli-produced HPV 16 and 18 vaccine or hepatitis E vaccine (control) and followed-up for 66 months. The primary outcomes were high-grade genital lesions and persistent infection (longer than 6 months) associated with HPV 16 or 18 in the per-protocol susceptible population. This trial was registered with ClinicalTrials.gov, NCT01735006.

Findings

Between Nov 22, 2012, and April 1, 2013, 8827 women were assessed for eligibility. 1455 women were excluded, and 7372 women were enrolled and randomly assigned to receive the HPV vaccine (n=3689) or control (n=3683). Vaccine efficacy was 100·0% (95% CI 67·2–100·0) against high-grade genital lesions (0 [0%] of 3310 participants in the vaccine group and 13 [0·4%] of 3302 participants in the control group) and 97·3% (89·9–99·7) against persistent infection (2 [0·1%] of 3262 participants in the vaccine group and 73 [2·2%] of 3271 participants in the control group) in the per-protocol population. Serious adverse events occurred at a similar rate between vaccine (267 [7·2%] of 3691 participants) and control groups (290 [7·9%] of 3681); none were considered related to vaccination.

Interpretation

The E coli-produced HPV 16 and 18 vaccine was well tolerated and highly efficacious against HPV 16 and 18 associated high-grade genital lesions and persistent infection and would supplement the global HPV vaccine availability and accessibility for cervical cancer prevention.

Funding

National Natural Science Foundation of China, National Key R&D Program of China, Fujian Provincial Project, Fundamental Funds for the Central Universities, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Xiamen Innovax.

更新日期：2022-08-26

点击分享查看原文

点击收藏

阅读更多本刊最新论文