Mapping immunological and host receptor binding determinants of SARS-CoV spike protein utilizing the Qubevirus platform.
Mapping immunological and host receptor binding determinants of SARS-CoV spike protein utilizing the Qubevirus platform.
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DOI：
10.1016/j.jbc.2023.105460
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发表时间：
2023-12
影响因子：
4.8
通讯作者：
Waffo, Alain Bopda
中科院分区：
文献类型：
--
作者：
Sanders, Carrie;Dzelamonyuy, Aristide;Ntemafack, Augustin;Alatoom, Nadia;Nchinda, Godwin;Georgiadis, Millie M.;Waffo, Alain Bopda
利用Qubevirus平台对SARS冠状病毒S蛋白的嗜性和免疫相互作用进行了研究。我们分别表明，代表S蛋白的14个重叠肽片段（每个100个残基的F1-14）可以插入重组Qubevirus上的A1的C末端而不影响其活力。此外，重组噬菌体表达导致不同工程化片段以可接近的方式暴露于表面。发现来自S425-525的F6含有重组人血管紧张素转换酶2的结合决定簇，其中最短的活性结合基序位于残基S437-492之间。上游，另一个片段F7，含有F6的重叠部分，不会与重组人血管紧张素转化酶2结合，证实了一段连续的残基可以采用F6的适当结构取向作为Qubevirus内的插入。F6（S441-460）和其他插入片段，包括F7/F8（S601-620）和F10（S781-800），通过识别和结合S蛋白特异性（抗S）抗体，被证明含有重要的免疫决定簇。带有所有三种抗S反应性表位的融合的工程化嵌合插入物实质上改善了对其同源抗体的识别和结合。这些结果提供了深入了解体液免疫相关表位和嗜性特征的S蛋白的亚单位疫苗或其他生物制剂的发展，对SARS冠状病毒的影响。
The motifs involved in tropism and immunological interactions of SARS-CoV spike (S) protein were investigated utilizing the Qubevirus platform. We showed that separately, 14 overlapping peptide fragments representing the S protein (F1-14 of 100 residues each) could be inserted into the C terminus of A1 on recombinant Qubevirus without affecting its viability. Additionally, recombinant phage expression resulted in the surface exposure of different engineered fragments in an accessible manner. The F6 from S425-525 was found to contain the binding determinant of the recombinant human angiotensin-converting enzyme 2, with the shortest active binding motif situated between residues S437-492. Upstream, another fragment, F7, containing an overlapping portion of F6 would not bind to recombinant human angiotensin-converting enzyme 2, confirming that a contiguous stretch of residues could adopt the appropriate structural orientation of F6 as an insertion within the Qubevirus. The F6 (S441-460) and other inserts, including F7/F8 (S601-620) and F10 (S781-800), were demonstrated to contain important immunological determinants through recognition and binding of S protein specific (anti-S) antibodies. An engineered chimeric insert bearing the fusion of all three anti-S reactive epitopes improved substantially the recognition and binding to their cognate antibodies. These results provide insights into humoral immune relevant epitopes and tropism characteristics of the S protein with implications for the development of subunit vaccines or other biologics against SARS-CoV.
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影响因子：
3.9
作者：
Callanan J;Stockdale SR;Adriaenssens EM;Kuhn JH;Rumnieks J;Pallen MJ;Shkoporov AN;Draper LA;Ross RP;Hill C
通讯作者：
Hill C
DOI：
10.1016/j.bbrc.2004.05.066
发表时间：
2004-07-02
影响因子：
3.1
作者：
Hua R;Zhou Y;Wang Y;Hua Y;Tong G
通讯作者：
Tong G
SARS-COV峰值蛋白的受体结合结构域可诱导高度有效的中和抗体：对开发亚基疫苗的影响。
DOI：
10.1016/j.bbrc.2004.09.106
发表时间：
2004-11-12
影响因子：
3.1
作者：
He Y;Zhou Y;Liu S;Kou Z;Li W;Farzan M;Jiang S
通讯作者：
Jiang S
DOI：
10.15585/mmwr.mm7008e1
发表时间：
2021-02-26
期刊：
MMWR. Morbidity and mortality weekly report
影响因子：
--
作者：
Firestone MJ;Lorentz AJ;Wang X;Como-Sabetti K;Vetter S;Smith K;Holzbauer S;Meyer S;Ehresmann K;Danila R;Lynfield R
通讯作者：
Lynfield R
影响因子：
3.7
作者：
Elshabrawy HA;Coughlin MM;Baker SC;Prabhakar BS
通讯作者：
Prabhakar BS