Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
Front Cell Infect Microbiol. 2020 Aug 26;10:442. doi: 10.3389/fcimb.2020.00442. eCollection 2020.
Melioidosis is a neglected tropical disease with high mortality rate. It is caused by the Gram-negative, CDC category B select agent () that is intrinsically resistant to first-line antibiotics. An antibody-based vaccine is likely to be the most effective control measure. Previous studies have demonstrated significant mechanistic roles of antibodies in protection against death in animal models, but data from human melioidosis is scarce. Herein, we used antibody-dependent cellular phagocytosis and growth inhibition assays to assess the mechanism of protective antibodies in patients with acute melioidosis. We found that serum from patients who survived the disease enable more live to be engulfed by THP-1 derived macrophages (median 1.7 × 10 CFU/ml, IQR 1.1 × 10-2.5 × 10 CFU/ml) than serum from patients who did not survive (median 1.2 × 10 CFU/ml, IQR 0.7 × 10-1.8 × 10, = 0.02). In addition, the intracellular growth rate of pre-opsonized with serum from survivors (median 7.89, IQR 5.58-10.85) was diminished when compared with those with serum from non-survivors (median 10.88, IQR 5.42-14.88, = 0.04). However, the difference of intracellular bacterial growth rate failed to reach statistical significance when using purified IgG antibodies ( = 0.09). These results provide new insights into a mechanistic role of serum in protection against death in human melioidosis for antibody-based vaccine development.
类鼻疽是一种高死亡率的被忽视热带病。它是由革兰氏阴性、疾病预防控制中心分类 B 选择剂 ()引起的,该细菌对一线抗生素具有固有耐药性。基于抗体的疫苗可能是最有效的控制措施。先前的研究表明,抗体在动物模型中对死亡的保护具有重要的机制作用,但人类类鼻疽的数据却很少。在此,我们使用抗体依赖性细胞吞噬和生长抑制试验来评估急性类鼻疽患者中保护性抗体的作用机制。我们发现,从幸存患者中获得的血清能使更多的活 被 THP-1 衍生的巨噬细胞吞噬(中位数 1.7×10 CFU/ml,IQR 1.1×10-2.5×10 CFU/ml),而非幸存患者的血清则更少(中位数 1.2×10 CFU/ml,IQR 0.7×10-1.8×10 ,= 0.02)。此外,与来自非幸存者的血清相比,来自幸存者的血清预调理的 (中位数 7.89,IQR 5.58-10.85)的细胞内生长速度降低,= 0.04)。然而,当使用纯化 IgG 抗体时,细胞内细菌生长速度的差异未达到统计学意义(= 0.09)。这些结果为基于抗体的疫苗开发提供了血清在人类类鼻疽中预防死亡的机制作用的新见解。