Potent Neutralization Antibodies Induced by a Recombinant Trimeric Spike Protein Vaccine Candidate Containing PIKA Adjuvant for COVID-19.
Potent Neutralization Antibodies Induced by a Recombinant Trimeric Spike Protein Vaccine Candidate Containing PIKA Adjuvant for COVID-19.
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含有 PIKA 佐剂的 COVID-19 重组三聚刺突蛋白候选疫苗诱导强效中和抗体
DOI：
10.3390/vaccines9030296
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发表时间：
2021-03-22
期刊：
影响因子：
7.8
通讯作者：
Zhou D
中科院分区：
文献类型：
--
作者：
Tong J;Zhu C;Lai H;Feng C;Zhou D
中和抗体对预防冠状病毒感染至关重要。引起最有效的中和抗体的免疫原结构仍在研究中。在这里，我们测试了三聚体的免疫原性，全长穗蛋白有2个脯氨酸突变，以保持其预融合构象。将CHO细胞表达的重组三聚体刺突蛋白与polyI:C （PIKA）佐剂一起免疫小鼠，接种时间为0 ~ 7 ~ 14 d。结果表明，在第21天诱导出了Spike特异性抗体，直接与Spike蛋白结合，平均滴度大于50,000。以中和IC50为1 μg/ml的单克隆抗体（40592-MM57和40591-MM43）为标准，用伪病毒系统检测，中和效价平均达到1000以上。蛋白/肽阵列显示，三聚体S蛋白疫苗诱导的抗体与自然感染相似，以受体结合域（RBD）为主要免疫优势区。RBD中未发现线性表位，但在RBD后的c端结构域和七肽重复区发现了几个线性表位。我们的研究支持了COVID-19重组三聚体刺突蛋白候选疫苗的有效性，该疫苗具有出色的安全性和在发展中国家储存和分发的准备性。
Neutralizing antibodies are critical to prevent corona virus infection. The structures of immunogens to elicit most potent neutralization antibodies are still under investigation. Here we tested the immunogenicity of the trimeric, full length Spike protein with 2 proline mutations to preserve its prefusion conformation. Recombinant trimeric Spike protein expressed by CHO cells was used with polyI:C (PIKA) adjuvant to immunize mice by 0-7-14 day schedule. The results showed that Spike-specific antibody was induced at day 21 with titer of more than 50,000 in average as measured by direct binding to Spike protein. The titer of neutralization reached more than 1000 in average when tested by a pseudo-virus system, using monoclonal antibodies (40592-MM57 and 40591-MM43) with neutralizing IC50 at 1 μg/ml as standards. Protein/peptide array showed that the antibodies induced by trimeric S protein vaccine bind similarly to natural infection with the receptor binding domain (RBD) as major immunodominant region. No linear epitopes were found in RBD, although several linear epitopes were found in C-terminal domain right after RBD, and heptad repeat regions. Our study supports the efficacy of recombinant trimeric Spike protein vaccine candidate for COVID-19, with excellent safety and readiness for storage and distribution in developing countries.
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影响因子：
5.5
作者：
Guebre-Xabier M;Patel N;Tian JH;Zhou B;Maciejewski S;Lam K;Portnoff AD;Massare MJ;Frieman MB;Piedra PA;Ellingsworth L;Glenn G;Smith G
通讯作者：
Smith G
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
158.5
作者：
Keech, Cheryl;Albert, Gary;Glenn, Gregory M.
通讯作者：
Glenn, Gregory M.
影响因子：
5.5
作者：
Chen WH;Tao X;Agrawal AS;Algaissi A;Peng BH;Pollet J;Strych U;Bottazzi ME;Hotez PJ;Lustigman S;Du L;Jiang S;Tseng CK
通讯作者：
Tseng CK
影响因子：
9.1
作者：
Cooper, CL;Davis, HL;Heathcote, J
通讯作者：
Heathcote, J