新冠灭活疫苗序贯免疫对Wuhan-Hu1和Omicron变异株的体液免疫反应

Sequential immunization with inactivated SARS-CoV-2 vaccines induces humoral immune responses against Wuhan-Hu1 and Omicron variants

目的研究新冠灭活疫苗序贯免疫策略对Wuhan-Hu1和Omicron变异株中和抗体的影响。方法BALB/c小鼠免疫两针Wuhan-Hu-1灭活疫苗,再分别用Omicron或Wuhan-Hu-1灭活疫苗加强免疫,采用酶联免疫吸附试验检测小鼠血清结合抗体水平;用水疱性口炎病毒假病毒检测系统检测小鼠血清中Omicron变异株中和抗体水平;采用酶联免疫吸附斑点实验检测特异性T细胞反应。结果与免疫一针Wuhan-Hu1灭活疫苗相比,免疫两针疫苗提高小鼠血清特异性Wuhan-Hu1、Delta和Omicron受体结合域(receptor binding domain,RBD)IgG滴度。与加强免疫Wuhan-Hu1灭活疫苗组相比,小鼠加强免疫Omicron灭活疫苗后,血清Wuhan-Hu1和Omicron特异性结合抗体RBD IgG GMT分别提高1.41和1.26倍;针对Omicron变异株BA.1、BA.2、BA.4/5和BF.7的中和抗体GMT分别提高4.5、3.4、12.1和6.5倍。加强免疫Wuhan-Hu1或Omicron灭活疫苗后,小鼠血清Wu-RBD IgA滴度高于免疫一针Wuhan-Hu1灭活疫苗(P=0.0057,P=0.0061)。结论加强免疫Omicron灭活疫苗能提高Omicron变异株的中和抗体水平。Wuhan-Hu1或Omicron灭活疫苗加强免疫能显著增强小鼠诱导的Wuhan-Hu1 RBD IgA。

Objective To explore the ability of sequential immunization regimen inducing neutralizing antibodies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Wuhan-Hu1 and Omicron variants in mice.Methods Groups of 6-8-week-old BALB/c mice were primed with two doses of Wuhan-Hu-1 inactivated vaccine,and then boosted with Omicron or Wuhan-Hu-1 inactivated vaccine,respectively.Binding antibodies were tested by enzyme linked immunosorbent assay;and neutralizing antibodies against Wuhan-Hu1 and Omicron variants were analyzed by vesicular stomatitis virus pseudovirus assay system;SARS-CoV-2 specific cellular immune responses were quantified by enzyme-linked immunosorbent spot assay.Results IgG antibodies against Wuhan-Hu1,Delta and Omicron RBD were enhanced after the second dose of Wuhan-Hu1 inactivated vaccine.Compared with Wuhan-Hu1 inactivated vaccine,the group boosted with Omicron inactivated vaccine improved Wu-RBD and Omic-RBD specific IgG antibodies 1.41 and 1.26 times,and serum neutralizing antibodies against BA.1,BA.2,BA.4/5 and BF.7 were elevated 4.5,3.4,12.1 and 6.5 folds,respectively,by sequential immunization.After booster immunization with inactivated Wuhan-Hu1 or Omicron vaccines,Wu-RBD IgA titer was significantly higher than that of one dose inactivated Wuhan-Hu1 vaccine(P=0.0057,P=0.0061).Conclusions Neutralizing antibodies against Omicron variants were enhanced by sequential immunization with Omicron inactivated vaccine.Specific IgA was significantly enhanced after the third dose of inactivated vaccine.