Vaccines, Immunoprophylaxis, and Immunotherapy for Coronaviruses

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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.