新型冠状病毒灭活疫苗对Beta和Delta变异株的交叉中和活性

Cross-neutralization of antibodies induced by inactivated SARS-CoV-2 vaccine against Beta and Delta variants

目的评估新型冠状病毒灭活疫苗免疫人群和小鼠血清对变异株(Delta株和Beta株)的交叉中和活性。方法各取20份人群常规两剂基础免疫血清、三剂加强免疫血清和两剂小鼠免疫血清作为实验材料,采用新型冠状病毒原型株、Delta和Beta变异株3株病毒,在生物安全三级实验室中采用微量中和试验检测中和抗体。通过分析不同稀释度血清对固定剂量病毒的中和活性,计算血清阳性率和抗体几何平均滴度(geometric mean titer,GMT),评估免疫血清的交叉中和水平。结果人免疫血清对不同变异株的阳性率均大于95%;基础免疫后,接种者血清对原型株、Delta和Beta变异株的中和抗体GMT分别为109、41和15,与原型株比较,针对Delta和Beta变异株的中和抗体GMT分别下降2.7倍和7.3倍;加强免疫后,接种者血清对原型株、Delta和Beta株的中和抗体GMT分别为446、190和86,与原型株比较,针对Delta和Beta变异株的中和抗体GMT分别下降2.3倍和5.2倍。小鼠免疫血清对不同变异株的阳性率均为100%;对原型株、Delta和Beta变异株的中和抗体GMT分别为2037、862和408,与原型株比较,针对Delta和Beta变异株的中和抗体GMT分别下降2.4倍和5.0倍。结论新型冠状病毒灭活疫苗免疫后的人群和小鼠血清均可对Delta和Beta变异株产生一定水平的中和保护,且人群加强免疫后可产生更高水平的中和抗体和交叉中和抗体,为该疫苗的临床应用和保护效果评估提供了重要参考。

Objective To evaluate the in vitro cross-neutralization of serum antibodies in human and mice immunized with inactivated SARS-CoV-2 vaccine against Delta and Beta variants.Methods Human serum samples after a second and a third dose of inactivated SARS-CoV-2 vaccine and mouse serum samples after a two-dose vaccination were collected.The neutralizing antibodies in the samples against SARS-CoV-2 strains of prototype,Delta and Beta variants were detected using micro-neutralization assay in biosafety levelⅢlaboratory.The seroconversion rates and geometric mean titers(GMTs)of antibodies were calculated.Results The seroconversion rates of antibodies in human serum samples against different SARS-CoV-2 strains were all above 95%.After two-dose vaccination,the GMTs of neutralizing antibodies against the prototype,Delta and Beta strains were 109,41 and 15,respectively.The GMTs decreased by 2.7 folds and 7.3 folds for the Delta and Beta variants as compared with the prototype strain.After the booster vaccination,the GMTs of neutralizing antibodies against the prototype,Delta and Beta strains were 446,190 and 86,respectively.The GMTs of neutralizing antibodies against Delta and Beta variants decreased by 2.3 folds and 5.2 folds as compared with that against the prototype strain.The seroconversion rates of antibodies against different SARS-CoV-2 strains in mouse serum samples were all 100%.The GMTs of neutralizing antibodies against the prototype,Delta and Beta strains were 2037,862 and 408,respectively.The GMTs decreased by 2.4 folds and 5.0 folds for the Delta and Beta variants.Conclusions Inactivated SARS-CoV-2 vaccine could induce a certain level of neutralizing antibodies against Delta and Beta variants in both human and mouse models.Moreover,a third dose of vaccine induced higher levels of neutralizing antibodies against Delta and Beta variants in human.This study provided valuable data for the clinical application and protective evaluation of the inactivated SARS-CoV-2 vaccine.