PDF(Pubmed)
Abstract：
There is a critical need to understand the effectiveness of serum elicited by different SARS-CoV-2 vaccines against SARS-CoV-2 variants. We describe the generation of reference reagents comprised of post-vaccination sera from recipients of different primary vaccines with or without different vaccine booster regimens in order to allow standardized characterization of SARS-CoV-2 neutralization in vitro. We prepared and pooled serum obtained from donors who received a either primary vaccine series alone, or a vaccination strategy that included primary and boosted immunization using available SARS-CoV-2 mRNA vaccines (BNT162b2, Pfizer and mRNA-1273, Moderna), replication-incompetent adenovirus type 26 vaccine (Ad26.COV2·S, Johnson and Johnson), or recombinant baculovirus-expressed spike protein in a nanoparticle vaccine plus Matrix-M adjuvant (NVX-CoV2373, Novavax). No subjects had a history of clinical SARS-CoV-2 infection, and sera were screened with confirmation that there were no nucleocapsid antibodies detected to suggest natural infection. Twice frozen sera were aliquoted, and serum antibodies were characterized for SARS-CoV-2 spike protein binding (estimated WHO antibody binding units/ml), spike protein competition for ACE-2 binding, and SARS-CoV-2 spike protein pseudotyped lentivirus transduction. These reagents are available for distribution to the research community (BEI Resources), and should allow the direct comparison of antibody neutralization results between different laboratories. Further, these sera are an important tool to evaluate the functional neutralization activity of vaccine-induced antibodies against emerging SARS-CoV-2 variants of concern. IMPORTANCE: The explosion of COVID-19 demonstrated how novel coronaviruses can rapidly spread and evolve following introduction into human hosts. The extent of vaccine- and infection-induced protection against infection and disease severity is reduced over time due to the fall in concentration, and due to emerging variants that have altered antibody binding regions on the viral envelope spike protein. Here, we pooled sera obtained from individuals who were immunized with different SARS-CoV-2 vaccines and who did not have clinical or serologic evidence of prior infection. The sera pools were characterized for direct spike protein binding, blockade of virus-receptor binding, and neutralization of spike protein pseudotyped lentiviruses. These sera pools were aliquoted and are available to allow inter-laboratory comparison of results and to provide a tool to determine the effectiveness of prior vaccines in recognizing and neutralizing emerging variants of concern.
摘要：
迫切需要了解由不同SARS-CoV-2疫苗引发的血清对SARS-CoV-2变体的有效性。我们描述了在有或没有不同疫苗加强方案的情况下，来自不同初级疫苗接受者的疫苗接种后血清组成的参考试剂的产生，以便在体外对SARS-CoV-2中和进行标准化表征。我们制备并汇集了从单独接受任一初级疫苗系列的供体获得的血清，或疫苗接种策略，包括使用可用的SARS-CoV-2mRNA疫苗（BNT162b2，Pfizer和mRNA-1273，Moderna）的初次和加强免疫，无复制能力的26型腺病毒疫苗（Ad26。COV2·S,约翰逊和约翰逊），或在纳米颗粒疫苗加基质-M佐剂(NVX-CoV2373,Novavax)中的重组杆状病毒表达的刺突蛋白。没有受试者有临床SARS-CoV-2感染史，和血清进行筛选，确认没有检测到提示自然感染的核衣壳抗体。两次冷冻血清被分开，和血清抗体的特征在于SARS-CoV-2刺突蛋白结合（估计WHO抗体结合单位/ml），刺突蛋白竞争ACE-2结合，和SARS-CoV-2刺突蛋白假型慢病毒转导。这些试剂可分配给研究界(BEI资源)，并且应该允许直接比较不同实验室之间的抗体中和结果。Further,这些血清是评估疫苗诱导的抗体针对新出现的值得关注的SARS-CoV-2变体的功能中和活性的重要工具.重要性：COVID-19的爆炸证明了新型冠状病毒在引入人类宿主后如何迅速传播和进化。由于浓度下降，疫苗和感染诱导的针对感染和疾病严重程度的保护程度随着时间的推移而降低。并且由于新出现的变体改变了病毒包膜刺突蛋白上的抗体结合区。这里,我们汇集了接受不同SARS-CoV-2疫苗免疫的个体的血清,这些个体没有既往感染的临床或血清学证据.对血清池进行了直接刺突蛋白结合的表征，阻断病毒-受体结合，和中和刺突蛋白假型慢病毒。这些血清池是等分的,可用于实验室间比较结果,并提供确定现有疫苗在识别和中和新出现的关注变体中的有效性的工具。
