Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models.
Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models.
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DOI：
10.1126/scitranslmed.abm0899
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发表时间：
2022-04-06
影响因子：
17.1
通讯作者：
中科院分区：
文献类型：
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作者：
结束严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的大流行的一个主要挑战是开发一种具有广泛保护性的疫苗，以增强长期免疫力。作为关键免疫原的病毒表面刺突（S）蛋白经常发生突变，保守表位被聚糖屏蔽。在这里，我们揭示了S蛋白糖基化对病毒感染性具有位点差异效应。我们发现肺上皮细胞产生的S蛋白具有与感染性增加相关的糖型。与完全糖基化的S蛋白相比，用修剪成单GlcNAc修饰状态（SMG）的N-聚糖免疫S蛋白引起了更强的免疫应答，并且对人血管紧张素转换酶2（hACE 2）转基因小鼠针对关注变体（VOC）的保护更好。此外，从SMG免疫的小鼠中鉴定出一种广泛中和的单克隆抗体，其可以中和野生型SARS-CoV-2和VOC，效力为亚皮摩尔。总之，这些结果表明，去除聚糖屏蔽以更好地暴露保守序列有可能成为开发广泛保护性SARS-CoV-2疫苗的有效且简单的方法。通过去除SARS-CoV-2 S蛋白中的聚糖屏蔽而开发的疫苗可以保护人们免受相关变体的感染。针对严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）的广泛中和抗体疫苗对于遏制正在进行的2019冠状病毒病（COVID-19）大流行至关重要。在此，Huang等人评估了酶促去除SARS-CoV-2刺突蛋白聚糖屏蔽物的免疫学影响。作者发现，用缺乏聚糖屏障的S蛋白（称为SMG）免疫仓鼠或小鼠，引起了强烈和广泛的免疫反应。接种疫苗的小鼠受到保护，免受相关α、γ和δ变体的攻击。从接种疫苗的动物分离的抗体也可以中和omicron变体。总之，这些数据支持进一步研究SMG作为候选SARS-CoV-2疫苗。
A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc–decorated state (SMG) elicited stronger immune responses and better protection for human angiotensin-converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from SMG-immunized mice that could neutralize wild-type SARS-CoV-2 and VOCs with subpicomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine. A vaccine developed by removing glycan shields in the SARS-CoV-2 S protein conferred protection against infection with variants of concern. Vaccines that elicit broadly neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will be essential for curbing the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, Huang et al. evaluated the immunological impact of enzymatically removing glycan shields from the SARS-CoV-2 spike (S) protein. The authors found that immunizing hamsters or mice with S protein lacking glycan shields, termed SMG, elicited robust and broadly reactive immune responses. Vaccinated mice were protected from challenge with the alpha, gamma, and delta variants of concern. Antibodies isolated from vaccinated animals could also neutralize the omicron variant. Together, these data support further investigation into SMG as a candidate SARS-CoV-2 vaccine.
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超越屏蔽：聚糖在SARS-COV-2尖峰蛋白中的作用。
影响因子：
18.2
作者：
Casalino L;Gaieb Z;Goldsmith JA;Hjorth CK;Dommer AC;Harbison AM;Fogarty CA;Barros EP;Taylor BC;McLellan JS;Fadda E;Amaro RE
通讯作者：
Amaro RE
影响因子：
64.5
作者：
Dejnirattisai W;Zhou D;Ginn HM;Duyvesteyn HME;Supasa P;Case JB;Zhao Y;Walter TS;Mentzer AJ;Liu C;Wang B;Paesen GC;Slon-Campos J;López-Camacho C;Kafai NM;Bailey AL;Chen RE;Ying B;Thompson C;Bolton J;Fyfe A;Gupta S;Tan TK;Gilbert-Jaramillo J;James W;Knight M;Carroll MW;Skelly D;Dold C;Peng Y;Levin R;Dong T;Pollard AJ;Knight JC;Klenerman P;Temperton N;Hall DR;Williams MA;Paterson NG;Bertram FKR;Siebert CA;Clare DK;Howe A;Radecke J;Song Y;Townsend AR;Huang KA;Fry EE;Mongkolsapaya J;Diamond MS;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
64.5
作者：
Corti D;Purcell LA;Snell G;Veesler D
通讯作者：
Veesler D
影响因子：
4.3
作者：
Eastman P;Swails J;Chodera JD;McGibbon RT;Zhao Y;Beauchamp KA;Wang LP;Simmonett AC;Harrigan MP;Stern CD;Wiewiora RP;Brooks BR;Pande VS
通讯作者：
Pande VS
DOI：
10.1107/s2059798319011471
发表时间：
2019-10-01
影响因子：
2.2
作者：
Liebschner, Dorothee;Afonine, Pavel V.;Adams, Paul D.
通讯作者：
Adams, Paul D.