Vaccines, Immunoprophylaxis, and Immunotherapy for Coronaviruses

患者发生亚临床至严重呼吸道感染，总体病死率为35.4%。宿主免疫功能的研究对于了解防止随后暴露于MERS的反应和流行率研究非常重要，重点是抗病毒抗体的测量。MERS-CoV抗体往往是短暂的，这使得这些研究变得困难。CoV特异性T细胞反应通常是长期存在的，但对MERS患者免疫反应的这一方面一无所知。我们在所有MERS幸存者中鉴定了MERS-CoV特异性CD 4和CD 8 T细胞应答，并通过测量肽刺激后的细胞因子表达来证明功能。中和抗体滴度与CD 4 T细胞反应相关，但与CD 8 T细胞反应无关。抗体滴度的大小预测其在MERS动物模型中的保护能力。抗体滴度和CD 4 T细胞应答较高的患者ICU停留时间较长，病毒脱落时间较长，需要通气。无法检测到或非常低的MERS-CoV特异性抗体应答的患者具有可测量的病毒特异性CD 8 T细胞应答，这些应答与患者总库中的应答无法区分。年龄、疾病严重程度、合并症和MERS-CoV特异性CD 8 T细胞应答之间未观察到相关性。

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.