新冠病毒感染和疫苗接种人群血清中和SARS样冠状病毒效果研究  

Neutralizing Efficacy Against SARS-like Coronaviruses in the Sera from COVID-19 Convalescents and Vaccine Recipients

作　　者：谢湘平 伍谦 王岐洁 XIE Xiangping;WU Qian;WANG Qije(Department of Infectious Diseases,Shaoyang Central Hospital,Shaoyang 422099,China;Xinning County People's Hospital,Shaoyang 422099,China;Sun Yat-sen University,Zhongshan School of Medicine,Guangzhou 510000,China;The First People's Hospital of Chenzhou,Chenzhou423000,China)

机构地区：[1]湖南省邵阳市中心医院,邵阳422099 [2]湖南省邵阳市新宁县人民医院,邵阳422099 [3]中山大学中山医学院,广州510000 [4]湖南省郴州市第一人民医院,郴州423000

出　　处：《病毒学报》2024年第6期1238-1245,共8页Chinese Journal of Virology

基　　金：邵阳市科技计划项目(项目号:2020GX76),题目:COVID-19康复患者免疫状态评价;邵阳市科技计划重点创新项目(项目号:2023GZ2016),题目:新冠疫苗诱导高效中和抗体的免疫机制研究;湖南省卫生健康委科研计划课题(项目号:B202303087545),题目:广谱交叉SARS-like冠状病毒的中和抗体筛选以及抗体特征研究;湖南省自然科学基金(项目号:2024JJ7468),题目:新冠康复患者长效免疫应答:浆细胞与TFH细胞应答动力学的持续性跟踪。

摘　　要：新冠病毒(SARS-CoV-2)给全球健康、社会和经济造成了严重危害,目前仍在流行并持续变异。因此,了解不同人群血清中的中和抗体水平以及该抗体交叉中和其他冠状病毒的能力,对后续的新冠防治工作具有重要意义。本研究采集了三组人群的血清样本:(1)27名接种了两针或三针灭活疫苗后再感染Omicron BA.5/BF.7突变株的人群(灭活疫苗+BA.5/BF.7感染人群);(2)23名感染SARS-CoV-2原始毒株后再接种两针或三针灭活疫苗的人群(原始株+灭活疫苗人群);(3)21名已接种灭活疫苗但无感染史的人群(灭活疫苗+未感染人群)。同时,构建SARS-CoV-2原始株、SARS-CoV和5种SARS样冠状病毒(RaTG13、GXP5L、SZ3、Civet007、WIV1)以及4种Omicron突变株(BA.5、BF.7、XBB.1.5、EG.5.1)的刺突蛋白(S)的假病毒系统,用于检测上述人群血清的中和能力。结果显示,三组人群对SARS-CoV-2原始株具有较高的中和活性,但对于其他冠状病毒株的中和滴度普遍降低。原始株+灭活疫苗以及灭活疫苗+未感染人群的血清能有效中和SARS-CoV-2原始株、SARS-CoV-1和其他SARS样冠状病毒,提示这些血清对于未来SARS样冠状病毒的溢出具有潜在预防作用。相比之下,灭活疫苗+BA.5/BF.7突破感染人群产生的中和抗体对于SARS-CoV-1、SZ3、Civet007、WIV1的交叉中和活性显著降低。值得警惕的是,Omicron突变株XBB.1.5和EG.5.1几乎完全逃逸了三组人群血清的中和作用。本研究评估了三个不同人群的血清对多种新冠突变株和SARS样冠状病毒的中和活性,为后续应对新冠持续流行和潜在SARS样冠状病毒溢出提供科学参考。The SARS-CoV-2 has had a profound impact on global health,society,and the economy,and continues to spread widely and mutate continuously.Understanding the levels of neutralizing antibodies in the sera of different populations,as well as their cross-neutralizing capacity against other coronaviruses,is critical for the future prevention and control of COVID-19.This study collected serum samples from three groups:(I)27 individuals who experienced breakthrough infections with Omicron BA.5/BF.7 after receiving two or three doses of an inactivated vaccine;(II)23 individuals who were infected with the original SARS-CoV-2 strain and subsequently received two or three doses of an inactivated vaccine;and(III)21 vaccinated individuals without prior infection.A pseudovirus system was developed using the spike(S)proteins of the original SARS-CoV-2strain,SARS-CoV-2 and five SARS-like coronaviruses(RaTG13,GXP5L,SZ3,Civet007,and WIV1),and four Omicron variants(BA.5,BF.7,XBB.1.5,and EG.5.1)to evaluate the antibody neutralizing capacity in the sera of these groups.The results showed that all three groups exhibited high neutralizing activity against the original SARS-CoV-2 strain.However,the neutralizing titers against other SARS-like coronaviruses were generally lower.The sera from individuals in groups II and III(those infected with the original strain or vaccinated without prior infection)demonstrated effective neutralization of both the original SARS-CoV-2strain,SARS-CoV-1 and other five SARS-like coronaviruses,suggesting potential preventive effects against future spillovers of SARS-like coronaviruses.In contrast,the neutralizing antibodies produced by individuals in group I(vaccinated and subsequently infected with Omicron BA.5/BF.7)exhibited lower cross-neutralizing activity against SARS-CoV-1,SZ3,Civet007,and WIV1.Of particular concern,the Omicron variants XBB.1.5 and EG.5.1 were almost completely resistant to neutralization by sera from all three groups.This study provides an assessment of the neutralizing activity of sera

关 键 词：SARS-CoV-2 康复者 突破感染 灭活疫苗 中和抗体 SARS样冠状病毒 

分 类 号：R373.1[医药卫生—病原生物学] R392.7[医药卫生—基础医学]