Longevity of antibody and T-cell responses against outer membrane antigens of Orientia tsutsugamushi in scrub typhus patients
Longevity of antibody and T-cell responses against outer membrane antigens of Orientia tsutsugamushi in scrub typhus patients
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DOI：
10.1038/emi.2017.106
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发表时间：
2017-12-20
影响因子：
13.2
通讯作者：
Cho, Nam-Hyuk
中科院分区：
文献类型：
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作者：
Ha, Na-Young;Kim, Yuri;Cho, Nam-Hyuk
恙虫病东方体感染引起的恙虫病是亚太区域一个严重的公共卫生问题，发病率不断上升，并有零星暴发。然而，人类对特定抗原的保护性免疫力对这种细菌的特征很差。此外，在早期疫苗试验中或甚至在自然感染后产生的免疫力不能持续很长时间，并且在各种基因型之间的交叉反应性很差。在这里，我们系统地研究了动力学和幅度的特异性适应性免疫对两个膜抗原，56 kDa的类型特异性抗原（TSA 56）和表面细胞抗原A（ScaA），参与细菌粘附和入侵的主机在64个恢复恙虫病患者。患者对细菌抗原的抗体应答通常是短暂的，并在恢复后2年降至基线水平。抗TSA 56 IgG应答主要由IgG 1和IgG 3亚类组成，并在恢复后持续长达1年，而ScaA特异性IgG主要由更短暂的IgG 1组成，其他亚类的应答有限。细胞免疫，包括CD 4和CD 8 T细胞特异性膜抗原，也迅速下降，从感染后1年，酶联免疫斑点（ELISPOT）测定和流式细胞术。抗原特异性适应性免疫的短寿命可能归因于有限的记忆反应，如在早期使用全细菌抗原的疫苗研究中所观察到的。最后，我们确定了TSA 56抗原中HLA-A*0201限制性和高度保守的CD 8 T细胞表位，这可能是评估抗O.恙虫病和开发有效的恙虫病疫苗。
Scrub typhus, caused by Orientia tsutsugamushi infection, has been a serious public health issue in the Asia-Pacific region, with rising incidence and sporadic outbreaks. However, human protective immunity against specific antigens has been poorly characterized for this bacterium. In addition, immunity produced in early vaccine trials or even after natural infections, did not last long and had poor cross-reactivity among various genotypes. Here, we systematically investigated the kinetics and magnitude of specific adaptive immunity against two membrane antigens, 56 kDa type-specific antigen (TSA56) and surface cell antigen A (ScaA), that are involved in bacterial adhesion and invasion of the host in 64 recovered scrub typhus patients. Antibody responses to the bacterial antigens in patients were generally short-lived and waned to baseline levels 2 years after recovery. The anti-TSA56 IgG responses were predominantly composed of the IgG1 and IgG3 subclasses and persisted for up to 1 year after recovery, whereas IgG specific to ScaA primarily consisted of more transient IgG1, with limited responses by other subclasses. Cellular immunity, including CD4 and CD8 T-cells specific to membrane antigens, also rapidly declined from 1 year after infection, as measured by enzyme-linked immunospot (ELISPOT) assays and flow cytometry. The short longevity of antigen-specific adaptive immunity might be attributable to limited memory responses, as observed in earlier vaccine studies using whole bacterial antigens. Finally, we identified HLA-A*0201-restricted and highly conserved CD8 T-cell epitopes in the TSA56 antigen, which may be valuable tools for assessing cellular immunity against O. tsutsugamushi and developing an effective scrub typhus vaccine.