用于大流行和新出现冠状病毒的中和抗体疫苗。

Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses.

机构信息

Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.

Department of Surgery, Duke University, Durham, NC, USA.

出版信息

Nature. 2021 Jun;594(7864):553-559. doi: 10.1038/s41586-021-03594-0. Epub 2021 May 10.

Abstract

Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2). Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses.

摘要

贝塔冠状病毒引发了严重急性呼吸综合征(SARS)和中东呼吸综合征,以及当前的 SARS 冠状病毒 2(SARS-CoV-2)大流行。能够诱导针对 SARS-CoV-2 和在动物中循环的贝塔冠状病毒的保护性免疫的疫苗有可能预防未来的大流行。在这里,我们表明,用与 SARS-CoV-2 的受体结合域缀合的纳米颗粒,并佐以 3M-052 和明矾免疫猕猴,会引发针对蝙蝠冠状病毒、SARS-CoV 和 SARS-CoV-2(包括 B.1.1.7、P.1 和 B.1.351 变体)的交叉中和抗体反应。用这些纳米颗粒给猕猴接种疫苗,可使 SARS-CoV-2 的 50%抑制性血清中和滴度(ID)达到 47,216(几何平均值),并可预防上呼吸道和下呼吸道的 SARS-CoV-2 感染。编码稳定跨膜刺突或单体受体结合域的核苷修饰 mRNA 也会引发针对 SARS-CoV 和蝙蝠冠状病毒的交叉中和抗体反应,尽管其滴度低于纳米颗粒。这些结果表明,当前基于 mRNA 的疫苗可能为预防未来的人畜共患贝塔冠状病毒爆发提供一些保护,并为针对多种(或所有)贝塔冠状病毒的疫苗的进一步开发提供了多聚体蛋白平台。

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