基于大肠杆菌表达的重组九价人乳头瘤病毒(HPV 6/11/16/18/31/33/45/52/58型)疫苗免疫原性和安全性的Ⅱ期临床试验

Immunogenicity and safety of an Escherichia coli-produced human papillomavirus(types 6/11/16/18/31/33/45/52/58)L1 virus-like-particle vaccine:a phase 2 double-blind,randomized,controlled trial

人乳头瘤病毒(HPV)16/18型双价疫苗(大肠埃希菌)已上市并通过世界卫生组织预认证.本研究通过一项随机双盲Ⅱ期临床试验评估其第二代HPV6/11/16/18/31/33/45/52/58型九价疫苗在18~45岁健康女性中的免疫原性和安全性.来自江苏省东台市的627名女性志愿者1:1随机分配至九价疫苗组(313人)或对照组(314人),并按照0、1、6月接种程序分别接种三剂1.0 mL(270μg)九价疫苗或空白佐剂,主要终点为第7月时血清抗体阳转率和抗体水平.结果显示,几乎所有疫苗组符合方案人群在第7月时出现针对9种HPV型别的血清中和抗体阳转,仅2人未发生HPV11型阳转,1人未发生HPV52型阳转.九价疫苗组和对照组的总体不良事件发生率分别为80.8%和72.9%,绝大多数不良事件症状轻微并很快恢复,未发生疫苗相关严重不良事件.该研究证明候选九价疫苗具有良好的安全性和免疫原性,支持在更大人群中进一步进行效力研究.

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 lg)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.