Hu Yue-Mei, Bi Zhao-Feng, Zheng Ya, Zhang Li, Zheng Feng-Zhu, Chu Kai, Li Ya-Fei, Chen Qi, Quan Jia-Li, Hu Xiao-Wen, Huang Xing-Cheng, Zhu Kong-Xin, Wang-Jiang Ya-Hui, Jiang Han-Min, Zang Xia, Liu Dong-Lin, Yang Chang-Lin, Pan Hong-Xing, Zhang Qiu-Fen, Su Ying-Ying, Huang Shou-Jie, Sun Guang, Huang Wei-Jin, Huang Yue, Wu Ting, Zhang Jun, Xia Ning-Shao
Jiangsu Provincial Center for Disease Control and Prevention, Public Health Research Institute of Jiangsu Province, Nanjing 210009, China.
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China; National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, Xiamen University, Xiamen 361102, China.
Sci Bull (Beijing). 2023 Oct 30;68(20):2448-2455. doi: 10.1016/j.scib.2023.09.020. Epub 2023 Sep 19.
The Escherichia coli-produced human papillomavirus (HPV) 16/18 bivalent vaccine (Cecolin) has received prequalification by the World Health Organization based on its high efficacy and good safety profile. We aimed to evaluate the immunogenicity and safety of the second-generation nonavalent HPV 6/11/16/18/31/33/45/52/58 vaccine (Cecolin 9) through the randomized, blinded phase 2 clinical trial. Eligible healthy women aged 18-45 years were randomly (1:1) allocated to receive three doses of 1.0 mL (270 µg) of Cecolin 9 or placebo with a 0-1-6-month schedule. The primary endpoint was the seroconversion rate and geometric mean titer of neutralizing antibodies (nAbs) one month after the full vaccination course (month 7). The secondary endpoint was the safety profile including solicited adverse reactions occurring within 7 d, adverse events (AEs) occurring within 30 d after each dose, and serious adverse events (SAEs) occurring during the 7-month follow-up period. In total, 627 volunteers were enrolled and randomly assigned to Cecolin 9 (n = 313) or placebo (n = 314) group in Jiangsu Province, China. Almost all participants in the per-protocol set for immunogenicity (PPS-I) seroconverted for nAbs against all the nine HPV types at month 7, while two failed to seroconvert for HPV 11 and one did not seroconvert for HPV 52. The incidence rates of total AEs in the Cecolin 9 and placebo groups were 80.8% and 72.9%, respectively, with the majority of them being mild and recovering shortly. None of the SAEs were considered related to vaccination. In conclusion, the E. coli-produced 9-valent HPV (9vHPV) vaccine candidate was well tolerated and immunogenic, which warrants further efficacy studies in larger populations.
由大肠杆菌生产的人乳头瘤病毒（HPV）16/18二价疫苗（希刻劳）因其高效和良好的安全性已获得世界卫生组织的预认证。我们旨在通过随机、盲法2期临床试验评估第二代九价HPV 6/11/16/18/31/33/45/52/58疫苗（希刻劳9）的免疫原性和安全性。符合条件的18至45岁健康女性被随机（1:1）分配接受三剂1.0 mL（270μg）的希刻劳9或安慰剂，接种程序为0-1-6月。主要终点是全程接种疫苗后1个月（第7个月）中和抗体（nAbs）的血清转化率和几何平均滴度。次要终点是安全性，包括接种后7天内出现的主动报告的不良反应、每次接种后30天内出现的不良事件（AE）以及7个月随访期内出现的严重不良事件（SAE）。在中国江苏省，共有627名志愿者入组并被随机分配到希刻劳9组（n = 313）或安慰剂组（n = 314）。在免疫原性符合方案集（PPS-I）中，几乎所有参与者在第7个月时针对所有九种HPV类型的nAbs均发生血清转化，而有两名参与者针对HPV 11未发生血清转化，一名参与者针对HPV 52未发生血清转化。希刻劳9组和安慰剂组的总AE发生率分别为80.8%和72.9%，其中大多数为轻度且很快恢复。没有SAE被认为与疫苗接种有关。总之，由大肠杆菌生产九价HPV（9vHPV）候选疫苗耐受性良好且具有免疫原性，值得在更大人群中进行进一步的疗效研究。
