Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
EBioMedicine. 2021 Nov;73:103626. doi: 10.1016/j.ebiom.2021.103626. Epub 2021 Oct 20.
Highly efficacious vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed. However, the emergence of viral variants that are more infectious than the earlier SARS-CoV-2 strains is concerning. Several of these viral variants have the potential to partially escape neutralizing antibody responses, warranting continued immune-monitoring.
We used a panel of 30 post-mRNA vaccination sera to determine neutralization and RBD and spike binding activity against a number of emerging viral variants. The virus neutralization was determined using authentic SARS-CoV-2 clinical isolates in an assay format that mimics physiological conditions.
We tested seven currently circulating viral variants of concern/interest, including the three Iota sublineages, Alpha (E484K), Beta, Delta and Lambda in neutralization assays. We found only small decreases in neutralization against Iota and Delta. The reduction was stronger against a sub-variant of Lambda, followed by Beta and Alpha (E484K). Lambda is currently circulating in parts of Latin America and was detected in Germany, the US and Israel. Of note, reduction in a receptor binding domain and spike binding assay that also included Gamma, Kappa and A.23.1 was negligible.
Taken together, these findings suggest that mRNA SARS-CoV-2 vaccines may remain effective against these viral variants of concern/interest and that spike binding antibody tests likely retain specificity in the face of evolving SARS-CoV-2 diversity.
This work is part of the PARIS/SPARTA studies funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. In addition, this work was also partially funded by the Centers of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C), the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384), by anonymous donors and by the Serological Sciences Network (SeroNet) in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. 75N91019D00024, Task Order No. 75N91020F00003.
针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的高效疫苗已经研发出来。然而,传染性比早期 SARS-CoV-2 菌株更强的病毒变体的出现令人担忧。其中一些病毒变体有可能部分逃避中和抗体反应,需要持续进行免疫监测。
我们使用了一组 30 种 mRNA 疫苗接种后的血清,以确定针对多种新兴病毒变体的中和以及 RBD 和刺突结合活性。使用模拟生理条件的测定方法,使用真实的 SARS-CoV-2 临床分离物来测定病毒中和作用。
我们在中和测定中测试了七种目前流行的关注/感兴趣的病毒变体,包括三个 Iota 亚谱系、Alpha(E484K)、Beta、Delta 和 Lambda。我们发现仅对 Iota 和 Delta 的中和作用略有下降。对 Lambda 的一个亚变体的减少更强,其次是 Beta 和 Alpha(E484K)。Lambda 目前在拉丁美洲部分地区流行,并在德国、美国和以色列检测到。值得注意的是,在包含 Gamma、Kappa 和 A.23.1 的受体结合域和刺突结合测定中,减少几乎可以忽略不计。
总的来说,这些发现表明 mRNA SARS-CoV-2 疫苗可能对这些关注/感兴趣的病毒变体仍然有效,并且在 SARS-CoV-2 多样性不断演变的情况下,刺突结合抗体测试可能仍然具有特异性。
这项工作是由 NIAID 合作流感疫苗创新中心 (CIVIC) 合同 75N93019C00051 资助的 PARIS/SPARTA 研究的一部分。此外,这项工作还部分得到了卓越流感研究与监测中心(CEIRS,合同# HHSN272201400008C)、JPB 基金会、开放慈善项目(研究赠款 2020-215611(5384))、匿名捐赠者以及血清学科学网络(SeroNet)的部分资助,后者部分由美国国立卫生研究院国家癌症研究所提供联邦资金,合同号为 75N91019D00024,任务订单号为 75N91020F00003。