【摘要】 目的 评价不同剂量、不同免疫程序的重组新型冠状病毒蛋白疫苗(CHO细胞)(ZF2001)在18～59岁健康人群中的免疫原性和持久性。方法 本研究为Ⅱ期临床试验，采用随机、盲法、安慰剂对照的研究设计，纳入900例18～59岁健康人群，按1∶1∶1∶1∶1∶1比例随机分配至低剂量2剂组、高剂量2剂组、安慰剂2剂组、低剂量3剂组、高剂量3剂组、安慰剂3剂组，接种ZF2001或安慰剂。采集所有研究对象不同时间节点血样进行新冠病毒原型株中和抗体、受体结合区域(receptor binding domain,RBD)蛋白结合抗体检测。结果 低剂量2剂组、高剂量2剂组、安慰剂2剂组全程接种后14 d和6个月中和抗体几何平均滴度(geometric mean titer, GMT)分别为17.7、14.1、2.0和3.6、3.7、2.0;RBD蛋白结合抗体GMT分别为439.82、338.04、5.98和63.62、50.42、5.67。低剂量3剂组、高剂量3剂组、安慰剂3剂组全程接种后14 d、6和12个月中和抗体GMT分别为97.3、68.4、2.0及19.3、16.7、2.0和7.4、7.3、2.0；全程接种后14 d、6个月RBD蛋白结合抗体GMT分别为1 745.67、1 107.36、5.84和281.31、212.41、5.80。结论 ZF2001在健康人群中可诱导较高的中和抗体及RBD蛋白结合抗体滴度，接种3剂次的免疫持久性优于2剂次，接种低剂量的免疫原性和免疫持久性优于高剂量，全程接种后6个月中和抗体呈现下降趋势。建议使用低剂量3剂接种程序，且在全程接种后6个月考虑加强接种。更多还原

【Abstract】 Objective To evaluate the immunogenicity and immune persistence of recombinant novel coronavirus protein vaccine(CHO cells),ZF2001,at different doses and immunization procedures in healthy people aged 18-59 years.Methods We conducted a randomized,blind,placebo-controlled and phase II clinical trial.A total of 900 healthy participants aged 18-59 years were randomly assigned to two-doses of low-dose group,two-doses of high-dose group,two-doses of placebo group,three-doses of low-dose group,three-doses of high-dose group,and three-doses of placebo group at a ratio of 1:1:1:1:1:1 and received ZF2001 or placebo.All the participants’ blood samples were collected for SARS-CoV-2 neutralizing and receptor binding domain(RBD)protein-binding antibodies detection before vaccination,14 days,six months,and 12 months after full vaccination.Results The geometric mean titers(GMTs)of neutralizing antibodies of two-doses of low-dose group,two-doses of high-dose group,two-doses of placebo group at 14 days after full vaccination were 17.7,14.1 and 2.0 respectively,and those at 6 months after full vaccination were 3.6,3.7 and 2.0 respectively.The GMTs of RBD protein-binding antibodies of the above-mentioned three groups at 14 days after full vaccination were 439.82,338.04 and 5.98 respectively,and those at 6 months after full vaccination were 63.62,50.42,and 5.67 respectively.The GMTs of neutralizing antibodies of three-doses of low-dose group,three-doses of high-dose group,and three-doses of placebo group at 14 days after full vaccination were 97.3,68.4 and 2.0respectively,those at 6 months after full vaccination were 19.3,16.7 and 2.0 respectively,and those at 12 months after full vaccination were 7.4,7.3 and 2.0 respectively.The GMTs of RBD protein-binding antibodies of the above-mentioned three groups at 14 days after full vaccination were 1,745.67,1,107.36 and 5.84 respectively,and those at 6 months after full vaccination were281.31,212.41 and 5.80 respectively.Conclusion ZF2001 can induce high levels of neutralizing and RBD protein-binding antibodies in the healthy participants.The immune persistence of three doses is better than that of two doses,and the immunogenicity and immune persistence of low doses are superior to those of high doses.The neutralizing antibodies at 6 months after full vaccination show a decreasing trend.A low-dose and three-dose vaccination program is recommended,and booster vaccination at 6 months after full vaccination should be considered.更多还原