MERS-CoV infection elicits long-lasting specific antibody, T and B cell immune responses in recovered individuals.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic zoonotic betacoronaviruses and a global public health concern. Better undersetting of the immune responses to MERS-CoV is needed to characterize the correlates of protection and durability of the immunity and to aid in developing preventative and therapeutic interventions. While MERS-CoV-specific circulating antibodies could persist for several years post-recovery, their waning raises concerns about their durability and role in protection. Nonetheless, memory B and T cells could provide long-lasting protective immunity despite the serum antibodies levels. METHODS: Serological and flow cytometric analysis of MERS-CoV-specific immune responses were performed on samples collected from a cohort of recovered individuals who required intensive care unit (ICU) admission as well as hospital or home isolation several years after infection to characterize the longevity and quality of humoral and cellular immune responses. RESULTS: Our data showed that MERS-CoV infection could elicit robust long-lasting virus-specific binding and neutralizing antibodies as well as T and B cell responses up to 6.9 years post-infection regardless of disease severity or need for ICU admission. Apart from the persistent high antibody titers, this response was characterized by B cell subsets with antibody-independent functions as demonstrated by their ability to produce TNF-α, IL-6, and IFN-γ cytokines in response to antigen stimulation. Furthermore, virus-specific activation of memory CD8+ and CD4+ T cell subsets from MERS-recovered patients resulted in secretion of high levels of TNF-α, IL-17 and IFN-γ. CONCLUSIONS: MERS-CoV infection could elicit robust long-lasting virus-specific humoral and cellular responses.

David versus goliath: ACE2-Fc receptor traps as potential SARS-CoV-2 inhibitors.

Anti-SARS-CoV-2 monoclonal antibodies and vaccines have shown improvement in lowering viral burden and hospitalization. However, emerging SARS-CoV-2 variants contain neutralizing antibody-escape mutations. Therefore, several reports have suggested the administration of recombinant angiotensin-converting enzyme 2 (rACE2) as a soluble receptor trap to block SARS-CoV-2 infection and limit viral escape potential. Several strategies have been implemented to enhance the efficacy of rACE2 as a therapeutic agent. Fc fusions have been used to improve pharmacokinetics and boost the affinity and avidity of ACE2 decoys for the virus spike protein. Furthermore, the intrinsic catalytic activity of ACE2 can be eliminated by introducing point mutations on the catalytic site of ACE2 to obtain an exclusive antiviral activity. This review summarizes different evolution platforms that have been used to enhance ACE2-Fc (i.e., immunoadhesins) as potential therapeutics for the current pandemic or future outbreaks of SARS-associated betacoronaviruses.

Seroprevalence of MERS-CoV in healthy adults in western Saudi Arabia, 2011-2016.

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly recognized zoonotic coronavirus. Current evidence confirms the role of dromedaries in primary human infections but does not explain the sporadic community cases. However, asymptomatic or subclinical cases could represent a possible source of infection in the community. METHODS: Archived human sera (7461) collected between 2011 and 2016 from healthy adult blood donors from 50 different nationalities in the western part of Saudi Arabia were obtained for MERS-CoV seroprevalence investigation. Samples were tested for MERS-CoV S1-specific antibodies (Abs) by ELISA and confirmed by testing for neutralizing Abs (nAbs) using both pseudotyped and live virus neutralization assays. RESULTS: Out of 7461 samples, 174 sera from individuals with 18 different nationalities were ELISA positive (2.3%, 95% CI 2.0-2.7). Presence of nAbs was confirmed in 17 samples (0.23%, 95% CI 0.1-0.4) of which one sample exhibited positivity in both neutralization assays. Confirmed seropositivity was identified in young (15-44 years) men and women from Saudi Arabia, Egypt, Yemen, Pakistan, Palestine, Sudan, and India without significant preference. CONCLUSIONS: An increasing trend of MERS-CoV seroprevalence was observed in the general population in western Saudi Arabia, suggesting that asymptomatic or mild infections might exist and act as an unrecognized source of infection. Seropositivity of individuals from different nationalities underscores the potential MERS exportation outside of the Arabian Peninsula. Thus, enhanced and continuous surveillance is highly warranted.