A 10 Year Long-Lived Cellular and Humoral MERS-CoV Immunity Cross-Recognizing the Wild-Type and Variants of SARS-CoV-2: A Potential One-Way MERS-CoV Cross-Protection Toward a Pan-Coronavirus Vaccine.

MERS is a respiratory disease caused by MERS-CoV. Multiple outbreaks have been reported, and the virus co-circulates with SARS-CoV-2. The long-term (> 6 years) cellular and humoral immune responses to MERS-CoV and their potential cross-reactivity to SARS-CoV-2 and its variants are unknown. We comprehensively investigated long-lasting MERS-CoV-specific cellular and humoral immunity, and its cross-reactivity against SARS-CoV-2 and its variants, in individuals recovered from MERS-CoV infection 1-10 years prior. Two cohorts of MERS-CoV survivors (31 unvaccinated, 38 COVID-19 vaccinated) were assessed for MERS-CoV IgG, memory CD4+/CD8+ T cells, and neutralizing antibodies against MERS-CoV and SARS-CoV-2 variants. MERS-CoV IgG levels and T cell responses were higher in the 1-5 vs 6-10 year postinfection groups. Vaccinated MERS-CoV survivors had significantly elevated MERS-CoV IgG and neutralization compared to unvaccinated. Both groups demonstrated cross-reactive neutralization of SARS-CoV-2 variants. MERS-CoV survivors vaccinated against SARS-CoV-2 had higher anti-MERS IgG, cellular immunity, and neutralization than unvaccinated survivors. MERS-CoV immune responses can persist for a decade. COVID-19 vaccination boosted humoral and cellular immunity in MERS-CoV survivors, suggesting the benefits of vaccination for this population. These findings have implications for pan-coronavirus vaccine development.