Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens.
Circularized Nanodiscs for Multivalent Mosaic Display of SARS-CoV-2 Spike Protein Antigens.
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DOI：
10.3390/vaccines11111655
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发表时间：
2023-10-28
期刊：
影响因子：
7.8
通讯作者：
Nasr ML
中科院分区：
文献类型：
--
作者：
Mabrouk MT;Zidan AA;Aly N;Mohammed MT;Ghantous F;Seaman MS;Lovell JF;Nasr ML
逃避疫苗的SARS-CoV-2变异体的出现促使人们需要能够引发广泛中和抗体（bnAb）的疫苗。在这里，我们评估了共价环化的纳米盘装饰与重组SARS-CoV-2刺突糖蛋白从几个变种引发bnAb与疫苗接种。将钴卟啉-磷脂（CoPoP）掺入纳米盘中以允许刺突三聚体通过其His-标签在纳米盘表面上的锚定和功能取向。将单磷酰脂质（MPLA）和QS-21作为免疫刺激佐剂并入以增强疫苗应答。优化后的nanodisces组装，刺突蛋白有效地显示在nanodisces的表面上，并保持其与人血管紧张素转换酶2（hACE 2）的结合，分别使用电子显微镜和狭缝印迹试验验证的构象能力。制备了6种不同的制剂，其中含有单抗原; 4种来自2020年（WT、Beta、Lambda和Delta），2种来自2021年（Omicron BA.1和BA.2）。此外，我们还制备了一个镶嵌纳米盘，展示了2020年的四种刺突蛋白。用镶嵌纳米盘肌内接种CD-1雌性小鼠诱导的抗体应答不仅中和了匹配的假型病毒，而且还中和了与2021年以后的变体（Omicron BA.1和BA.2）相对应的错配假型病毒。有趣的是，来自嵌合免疫小鼠的血清不能有效抑制Omicron刺突与人ACE-2的结合，这表明一些引发的抗体针对受体结合结构域之外的保守中和表位。我们的研究结果表明，从2020年开始展示刺突蛋白的镶嵌纳米盘疫苗可以引发广泛中和抗体，这些抗体可以中和第二年的错配病毒，从而减少新出现的变异的免疫逃避并增强医疗准备。
The emergence of vaccine-evading SARS-CoV-2 variants urges the need for vaccines that elicit broadly neutralizing antibodies (bnAbs). Here, we assess covalently circularized nanodiscs decorated with recombinant SARS-CoV-2 spike glycoproteins from several variants for eliciting bnAbs with vaccination. Cobalt porphyrin–phospholipid (CoPoP) was incorporated into the nanodisc to allow for anchoring and functional orientation of spike trimers on the nanodisc surface through their His-tag. Monophosphoryl-lipid (MPLA) and QS-21 were incorporated as immunostimulatory adjuvants to enhance vaccine responses. Following optimization of nanodisc assembly, spike proteins were effectively displayed on the surface of the nanodiscs and maintained their conformational capacity for binding with human angiotensin-converting enzyme 2 (hACE2) as verified using electron microscopy and slot blot assay, respectively. Six different formulations were prepared where they contained mono antigens; four from the year 2020 (WT, Beta, Lambda, and Delta) and two from the year 2021 (Omicron BA.1 and BA.2). Additionally, we prepared a mosaic nanodisc displaying the four spike proteins from year 2020. Intramuscular vaccination of CD-1 female mice with the mosaic nanodisc induced antibody responses that not only neutralized matched pseudo-typed viruses, but also neutralized mismatched pseudo-typed viruses corresponding to later variants from year 2021 (Omicron BA.1 and BA.2). Interestingly, sera from mosaic-immunized mice did not effectively inhibit Omicron spike binding to human ACE-2, suggesting that some of the elicited antibodies were directed towards conserved neutralizing epitopes outside the receptor binding domain. Our results show that mosaic nanodisc vaccine displaying spike proteins from 2020 can elicit broadly neutralizing antibodies that can neutralize mismatched viruses from a following year, thus decreasing immune evasion of new emerging variants and enhancing healthcare preparedness.
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DOI：
10.3390/pathogens11091035
发表时间：
2022-09-12
期刊：
Pathogens (Basel, Switzerland)
影响因子：
--
作者：
通讯作者：
--
影响因子：
38.3
作者：
Huang WC;Deng B;Lin C;Carter KA;Geng J;Razi A;He X;Chitgupi U;Federizon J;Sun B;Long CA;Ortega J;Dutta S;King CR;Miura K;Lee SM;Lovell JF
通讯作者：
Lovell JF
影响因子：
64.5
作者：
Garcia-Beltran, Wilfredo F.;St Denis, Kerri J.;Balazs, Alejandro B.
通讯作者：
Balazs, Alejandro B.
影响因子：
3.7
作者：
Elshabrawy HA;Coughlin MM;Baker SC;Prabhakar BS
通讯作者：
Prabhakar BS
单磷酰脂质 A (MPLA) 是灭活狂犬病疫苗的有效佐剂
影响因子：
4.7
作者：
Chen, Chen;Zhang, Chengguang;Zhao, Ling
通讯作者：
Zhao, Ling