一种自主生产的9价人乳头瘤病毒L1病毒样颗粒疫苗（6/11/16/18/31/33/45/52/58型）在健康成年人中的安全性和免疫原性：一项开放标签、剂量递增的1期临床试验。
Safety and immunogenicity of an -produced 9-valent human papillomavirus L1 virus-like particle vaccine (types 6/11/16/18/31/33/45/52/58) in healthy adults: an open-label, dose-escalation phase 1 clinical trial.
作者信息
Chu Kai, Bi Zhao-Feng, Huang Wei-Jin, Li Ya-Fei, Zhang Li, Yang Chang-Lin, Jiang Han-Min, Zang Xia, Chen Qi, Liu Dong-Lin, Pan Hong-Xing, Huang Yue, Zheng Feng-Zhu, Zhang Qiu-Fen, Sun Guang, Su Ying-Ying, Huang Shou-Jie, Pan Hui-Rong, Wu Ting, Hu Yue-Mei, Zhang Jun, Zhu Feng-Cai, Xia Ning-Shao
机构信息
Jiangsu Provincial Center for Disease Control and Prevention, Public Health Research Institute of Jiangsu Province, Nanjing, Jiangsu, 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, Xiamen University, Xiamen, Fujian, China.
出版信息
Lancet Reg Health West Pac. 2023 Mar 13;34:100731. doi: 10.1016/j.lanwpc.2023.100731. eCollection 2023 May.
BACKGROUND
A safe and highly efficacious ()-produced HPV 16/18 bivalent vaccine has been prequalified by the World Health Organization. Here, we conducted a single-center, open-label, dose-escalation phase 1 clinical trial to evaluate the safety and immunogenicity of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine.
METHOD
Twenty-four eligible volunteers aged 18-45 years were enrolled in January 2019 in Dongtai, China and received 0.5 mL (135 μg) or 1.0 mL (270 μg) of the candidate vaccine with a 0/1/6-month dose-escalation schedule. Local and systemic adverse events (AEs) occurring within 30 days after each vaccination and serious adverse events (SAEs) occurring within 7 months were recorded. Blood samples from each participant were collected before and 2 days after the first and third vaccinations to determine changes in laboratory parameters. Serum IgG and neutralizing antibody (nAb) levels against each HPV type at month 7 were analyzed (ClinicalTrials.gov: NCT03813940).
FINDINGS
The incidences of total AEs in the 135 μg and 270 μg groups were 66.7% and 83.3%, respectively. All AEs were mild or moderate, and no SAEs were reported. No clinically significant changes were found in paired blood indices before or after any of the vaccinations. All the participants in the per-protocol set except for two who failed to seroconvert for HPV 11 or 58 in the 135 μg group seroconverted at month 7 for both IgG and nAbs.
INTERPRETATION
The candidate -produced 9vHPV vaccine has been preliminarily proven to be well tolerated and immunogenic, which encourages further studies in large cohorts with a wider age range.
FUNDING
This study was supported by the National Natural Science Foundation of China, Fujian Provincial Natural Science Foundation, Fujian Province Health and Education Joint Research Program, Xiamen Science and Technology Plan Project, Fundamental Research Funds for the Central Universities, CAMS Innovation Fund for Medical Sciences of China, and Xiamen Innovax Biotechnology Co., Ltd.
背景
一种安全且高效的（）生产的人乳头瘤病毒16/18二价疫苗已获得世界卫生组织的预认证。在此，我们开展了一项单中心、开放标签、剂量递增的1期临床试验，以评估第二代九价人乳头瘤病毒6/11/16/18/31/33/45/52/58疫苗的安全性和免疫原性。
方法
2019年1月，在中国东台招募了24名年龄在18至45岁之间的符合条件的志愿者，按照0/1/6月的剂量递增方案，给予0.5毫升（135微克）或1.0毫升（270微克）的候选疫苗。记录每次接种后30天内发生的局部和全身不良事件（AE）以及7个月内发生的严重不良事件（SAE）。在首次和第三次接种前及接种后2天采集每位参与者的血样，以确定实验室参数的变化。分析第7个月时针对每种人乳头瘤病毒类型的血清IgG和中和抗体（nAb）水平（ClinicalTrials.gov：NCT03813940）。
结果
135微克组和270微克组的总不良事件发生率分别为66.7%和83.3%。所有不良事件均为轻度或中度，未报告严重不良事件。在任何一次接种前后的配对血液指标中均未发现具有临床意义的变化。在符合方案集中，除135微克组中有两名参与者未实现人乳头瘤病毒11或58血清转化外，所有参与者在第7个月时IgG和nAb均实现了血清转化。
解读
候选的（）生产的9vHPV疫苗已初步证明耐受性良好且具有免疫原性，这鼓励在更广泛年龄范围的大型队列中开展进一步研究。
资金
本研究得到了中国国家自然科学基金、福建省自然科学基金、福建省卫生与教育联合研究项目、厦门市科技计划项目、中央高校基本科研业务费、中国医学科学院医学与健康科技创新工程以及厦门万泰沧海生物技术有限公司的支持。
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