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含有 D614G 和 BA.1 刺突三聚体蛋白的二价疫苗或 BA.1 刺突三聚体蛋白加强针可产生广泛的中和免疫。

A bivalent vaccine containing D614G and BA.1 spike trimer proteins or a BA.1 spike trimer protein booster shows broad neutralizing immunity.

机构信息

Genetic Testing Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Department of Blood Transfusion and Clinical Lab, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

出版信息

J Med Virol. 2022 Sep;94(9):4287-4293. doi: 10.1002/jmv.27885. Epub 2022 Jun 2.

DOI:10.1002/jmv.27885
PMID:35614524
Abstract

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, sublineages BA.1 and BA.2, recently became the dominant variants of concern (VOCs) with significantly higher transmissibility than any other variant appeared and markedly greater resistance to neutralization antibodies and original ancestral WA1 spike-matched vaccine. Therefore, it is urgent to develop vaccines against VOCs like Omicron. Unlike the new booming messenger RNA (mRNA) vaccine, protein vaccines have been used for decades to protect people from various kinds of viral infections and have advantages with their inexpensive production protocols and their relative stability in comparison to the mRNA vaccine. Here, we show that sera from BA.1 spike protein vaccinated mice mainly elicited neutralizing antibodies against BA.1 itself. However, a booster with BA.1 spike protein or a bivalent vaccine composed of D614G and BA.1 spike protein-induced not only potent neutralizing antibody response against D614G and BA.1 pseudovirus, but also against BA.2, other four SARS-CoV-2 VOCs (Alpha, Beta, Gamma, and Delta) and SARS-CoV-2-related coronaviruses (pangolin CoV GD-1 and bat CoV RsSHC014). The two recombinant spike protein vaccines method described here lay a foundation for future vaccine development for broad protection against pan-sarbecovirus.

摘要

新出现的严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)奥密克戎变异株,亚谱系 BA.1 和 BA.2,最近成为主要关注的变异株(VOCs),其传染性明显高于任何其他出现的变异株,并且对中和抗体和原始祖先 WA1 刺突匹配疫苗的抗性明显更高。因此,迫切需要开发针对奥密克戎等 VOC 的疫苗。与新兴的信使 RNA(mRNA)疫苗不同,蛋白疫苗已被使用数十年,用于保护人们免受各种病毒感染,并且具有与 mRNA 疫苗相比生产成本低廉且相对稳定的优势。在这里,我们表明,接种 BA.1 刺突蛋白的小鼠血清主要诱导针对 BA.1 自身的中和抗体。然而,用 BA.1 刺突蛋白进行加强免疫或由 D614G 和 BA.1 刺突蛋白组成的二价疫苗不仅诱导了针对 D614G 和 BA.1 假病毒的强大中和抗体反应,而且还诱导了针对 BA.2、其他四种 SARS-CoV-2 VOCs(Alpha、Beta、Gamma 和 Delta)和 SARS-CoV-2 相关冠状病毒(穿山甲 CoV GD-1 和蝙蝠 CoV RsSHC014)的中和抗体反应。这里描述的两种重组刺突蛋白疫苗方法为未来针对泛 SARS-CoV 的广泛保护开发疫苗奠定了基础。

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