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

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. Here, we obtained PBMCs 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 ICU stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8 T cell responses comparable to those of the whole cohort. There were no correlations between age, disease severity, co-morbidities 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.

Middle East respiratory syndrome

“…49,57 Studies of MERS survivors showed that MERS-CoV-specific antibody responses tended to be lower and transient in patients with mild or subclinical disease when compared with patients with severe disease, in whom MERS-CoV-specific antibody responses were detected for at least 2 years. [57][58][59][60] In contrast, T-cell responses were detected in all MERS survivors for at least 2 years. 59 The transitory nature of the antibody response in mild disease and greater stability of the T-cell response suggest that induction of both will be required for optimal longterm protection; the measurement of both will enhance the accuracy of prevalence studies.…”

“…[57][58][59][60] In contrast, T-cell responses were detected in all MERS survivors for at least 2 years. 59 The transitory nature of the antibody response in mild disease and greater stability of the T-cell response suggest that induction of both will be required for optimal longterm protection; the measurement of both will enhance the accuracy of prevalence studies.…”

Heterologous prime–boost vaccination with adenoviral vector and protein nanoparticles induces both Th1 and Th2 responses against Middle East respiratory syndrome coronavirus

“…A recent study analyzing patients who survived MERS virus infection demonstrated that survival depended on induction of both a cell-mediated immune response and neutralizing antibody [36]. The analysis showed a correlation between the severity of symptoms, the activation of T cells extracted from peripheral blood mononuclear cells, and the intensity of the antibody response.…”

Factors associated with recovery delay in a sample of patients diagnosed by MERS‐CoV rRT‐PCR: A Saudi Arabian multicenter retrospective study

“…First, the study was based on chart reviews, and findings should be interpreted with caution. Second, we did not collect information on the type of antiviral treatment or other supportive treatments given after diagnosis which may have affected clinical outcomes . Third, despite this being the first investigation in this population, including a number of potential predictors for recovery delay, additional relevant predictors should be explored, such as the level of camel exposure, for example, hospital‐acquired infections.…”