Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses

中东呼吸综合征的康复与抗体和 T 细胞反应有关

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作者:Jingxian Zhao, Abeer N Alshukairi, Salim A Baharoon, Waleed A Ahmed, Ahmad A Bokhari, Atef M Nehdi, Laila A Layqah, Mohammed G Alghamdi, Manal M Al Gethamy, Ashraf M Dada, Imran Khalid, Mohamad Boujelal, Sameera M Al Johani, Leatrice Vogel, Kanta Subbarao, Ashutosh Mangalam, Chaorong Wu, Patrick Ten

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4+ and CD8+ T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT50) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4+ but not CD8+ T cell responses; patients with higher PRNT50 and CD4+ T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8+ T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8+ T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.

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