Sensitive and Specific Detection of Low-Level Antibody Responses in Mild Middle East Respiratory Syndrome Coronavirus Infections

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) infections in humans can cause asymptomatic to fatal lower respiratory lung disease. Despite posing a probable risk for virus transmission, asymptomatic to mild infections can go unnoticed; a lack of seroconversion among some PCR-confirmed cases has been reported. We found that a MERS-CoV spike S1 protein–based ELISA, routinely used in surveillance studies, showed low sensitivity in detecting infections among PCR-confirmed patients with mild clinical symptoms and cross-reactivity of human coronavirus OC43–positive serum samples. Using in-house S1 ELISA and protein microarray, we demonstrate that most PCR-confirmed MERS-CoV case-patients with mild infections seroconverted; nonetheless, some of these samples did not have detectable levels of virus-neutralizing antibodies. The use of a sensitive and specific serologic S1-based assay can be instrumental in the accurate estimation of MERS-CoV prevalence.

Development and Validation of a S1 Protein-Based ELISA for the Specific Detection of Antibodies against Equine Coronavirus

“…Our findings validate that ECoV S1 is a highly suitable antigen for the detection of antibodies against ECoV showing very good agreement between the ELISA and VN assays. Recently, similar conclusions were also drawn for the role of MERS S1 in MERS serology [31].…”

Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels

“…Nonetheless, non-neutralising S-specific Abs could also interfere with MERS-CoV entry and fusion in a similar manner to stem-specific anti-influenza hemagglutinin Abs 38 , but this has not yet been assessed for MERS-CoV. Similarly, S1-based ELISA have shown excellent correlation with live virus neutralization assay although both nAbs as well as non-neutralising binding Abs could be detected by ELISA 39,40 . In the current study, we found that induction of S1-binding non-neutralising Abs alone is insufficient to reduce viral shedding and only the presence of nAbs can minimise virus excretion.…”

Middle East respiratory syndrome

“…86 Several serological assays are available for detection of MERS-CoV: ELISA, recombinant spike immunofluorescent assay, and spike pseudoparticle neutralisation and microneutralisation assay. [87][88][89][90] A case confirmed by serology requires evidence of seroconversion in two samples, ideally taken at least 14 days apart, by a screening (eg, ELISA, immunofluorescence assay) and a neutralisation assay. 77,78 Imaging A range of abnormal but non-specific chest x-ray findings are seen in patients with MERS.…”