Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Department of Medicine, Mukdahan Hospital, Mukdahan, Thailand.
Front Immunol. 2021 Jul 30;12:698303. doi: 10.3389/fimmu.2021.698303. eCollection 2021.
Melioidosis, caused by the Gram-negative bacterium , is a serious infectious disease with diverse clinical manifestations. The morbidity and mortality of melioidosis is high in Southeast Asia and no licensed vaccines currently exist. This study was aimed at evaluating human cellular and humoral immune responses in Thai adults against four melioidosis vaccine candidate antigens. Blood samples from 91 melioidosis patients and 100 healthy donors from northeast Thailand were examined for immune responses against Hcp1, AhpC, TssM and LolC using a variety of cellular and humoral immune assays including IFN-γ ELISpot assays, flow cytometry and ELISA. PHA and a CPI peptide pool were also used as control stimuli in the ELISpot assays. Hcp1 and TssM stimulated strong IFN-γ secreting T cell responses in acute melioidosis patients which correlated with survival. High IFN-γ secreting CD4 T cell responses were observed during acute melioidosis. Interestingly, while T cell responses of melioidosis patients against the CPI peptide pool were low at the time of enrollment, the levels increased to the same as in healthy donors by day 28. Although high IgG levels against Hcp1 and AhpC were detected in acute melioidosis patients, no significant differences between survivors and non-survivors were observed. Collectively, these studies help to further our understanding of immunity against disease following natural exposure of humans to as well as provide important insights for the selection of candidate antigens for use in the development of safe and effective melioidosis subunit vaccines.
类鼻疽是由革兰氏阴性细菌引起的一种严重的传染病，具有多种临床表现。在东南亚，类鼻疽的发病率和死亡率很高，目前尚无许可的疫苗。本研究旨在评估泰国成年人对四种类鼻疽候选疫苗抗原的细胞和体液免疫反应。来自泰国东北部的 91 名类鼻疽患者和 100 名健康献血者的血液样本，通过使用各种细胞和体液免疫检测方法，包括 IFN-γ ELISpot 检测、流式细胞术和 ELISA，来检测针对 Hcp1、AhpC、TssM 和 LolC 的免疫反应。PHA 和 CPI 肽库也被用作 ELISpot 检测中的对照刺激物。Hcp1 和 TssM 在急性类鼻疽患者中刺激强烈的 IFN-γ 分泌 T 细胞反应，与存活相关。在急性类鼻疽期间观察到高 IFN-γ 分泌 CD4 T 细胞反应。有趣的是，虽然类鼻疽患者对 CPI 肽库的 T 细胞反应在入组时较低，但到第 28 天，其水平增加到与健康供体相同。虽然在急性类鼻疽患者中检测到针对 Hcp1 和 AhpC 的高 IgG 水平，但在幸存者和非幸存者之间未观察到显著差异。总之，这些研究有助于进一步了解人类自然暴露于 后对疾病的免疫反应，并为选择候选抗原用于开发安全有效的类鼻疽亚单位疫苗提供重要见解。
