Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Cell Rep. 2023 Apr 25;42(4):112402. doi: 10.1016/j.celrep.2023.112402. Epub 2023 Apr 15.
The 2013 Ebola epidemic in Central and West Africa heralded the emergence of wide-spread, highly pathogenic viruses. The successful recombinant vector vaccine against Ebola (rVSVΔG-ZEBOV-GP) will limit future outbreaks, but identifying mechanisms of protection is essential to protect the most vulnerable. Vaccine-induced antibodies are key determinants of vaccine efficacy, yet the mechanism by which vaccine-induced antibodies prevent Ebola infection remains elusive. Here, we exploit a break in long-term vaccine efficacy in non-human primates to identify predictors of protection. Using unbiased humoral profiling that captures neutralization and Fc-mediated functions, we find that antibodies specific for soluble glycoprotein (sGP) drive neutrophil-mediated phagocytosis and predict vaccine-mediated protection. Similarly, we show that protective sGP-specific monoclonal antibodies have elevated neutrophil-mediated phagocytic activity compared with non-protective antibodies, highlighting the importance of sGP in vaccine protection and monoclonal antibody therapeutics against Ebola virus.
2013 年中非和西非的埃博拉疫情标志着广泛存在的高致病性病毒的出现。针对埃博拉的成功重组载体疫苗（rVSVΔG-ZEBOV-GP）将限制未来的疫情爆发，但确定保护机制对于保护最脆弱的人群至关重要。疫苗诱导的抗体是疫苗功效的关键决定因素，但疫苗诱导的抗体预防埃博拉感染的机制仍然难以捉摸。在这里，我们利用非人类灵长类动物中疫苗长期功效的中断来确定保护的预测因子。通过利用能够捕获中和和 Fc 介导功能的无偏倚的体液分析，我们发现针对可溶性糖蛋白（sGP）的抗体特异性驱动中性粒细胞介导的吞噬作用，并预测疫苗介导的保护。同样，我们表明，保护性 sGP 特异性单克隆抗体具有比非保护性抗体更高的中性粒细胞介导的吞噬活性，突出了 sGP 在疫苗保护和针对埃博拉病毒的单克隆抗体治疗中的重要性。
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