Vaccines, Immunoprophylaxis, and Immunotherapy for Coronaviruses

患者发生亚临床至严重呼吸道感染，总病死率为35.4%。宿主免疫功能的研究，对于了解预防随后暴露于MERS的反应和流行率研究非常重要，主要集中在抗病毒抗体的测量上。MERS冠状病毒抗体往往是暂时性的，这使得这些研究变得困难。冠状病毒特异性的T细胞反应通常是长寿的，但对MERS患者的这一方面的免疫反应一无所知。我们在所有MERS幸存者中确定了MERS冠状病毒特异性的CD4和CD8T细胞反应，并通过测量多肽刺激后细胞因子的表达来证明其功能。中和抗体效价与CD4T细胞应答相关，但与CD8T细胞应答无关。在MERS动物模型中，抗体滴度的大小可以预测其保护能力。抗体滴度和CD4T细胞应答较高的患者在ICU停留的时间更长，病毒排出的时间更长，需要呼吸机。MERS冠状病毒特异性抗体反应不可检测或非常低的患者有可测量的病毒特异性CD8 T细胞反应，与患者总数的反应难以区分。未观察到年龄、疾病严重程度、合并症和MERS冠状病毒特异性CD8 T细胞反应之间的相关性。

Patients develop subclinical to severe respiratory tract infections, with an overall 35.4% case fatality rate. Studies of host immune function, important for understanding responses that protect against subsequent exposure to MERS and for prevalence studies have focused on measurements of anti-virus antibody. MERS-CoV antibodies tend to be transient, making these studies difficult. CoV-specific T cell responses are generally long-lived but nothing is known about this aspect of the immune response in MERS patients. We identified MERS-CoV-specific CD4 and CD8 T cell responses in all MERS survivors, and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing antibody titers correlated with CD4 T cell responses, but not with CD8 T cell responses. The magnitude of the antibody titer predicted its protective ability in an animal model of MERS. Patients with higher antibody titers and CD4 T cell responses had longer ICU stays, shed virus for a longer time and required ventilation. Patients with undetectable or very low MERS-CoV-specific antibody responses had measurable virus-specific CD8 T cell responses that were indistinguishable from those of the total pool of patients. No correlations were observed between age, disease severity, comorbidities and MERS-CoV-specific CD8 T cell responses.