Sustained Responses of Neutralizing Antibodies Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Recovered Patients and Their Therapeutic Applicability

Abstract

Background Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridge this gap. Methods We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered MERS-CoV patients for three years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge. Results Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients that suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than two fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining high neutralizing titer (> 1/5,000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss. Conclusions High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.

Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses

“…While levels of neutralizing antibodies to MERS-CoV were reported to remain stable for > 2 years (35), for SARS-CoV-2, it is now recognized, that antibody levels are already declining after 3 months (36,37). Therefore, identifying potential COVID-19 plasma donors is underlying additional time constraints.…”

Longevity of seropositivity and neutralizing antibodies in recovered MERS patients: a 5-year follow-up study

“…Despite the catastrophic impact of coronaviruses on public health worldwide, few effective therapeutic options are available for the diseases caused by these viruses [ 3 ]. Immune serum or plasma samples collected from recovered patients have been found to retain neutralizing activity in clinical therapeutic applications [ [4] , [5] , [6] , [7] ]. However, knowledge of the long-term dynamics and durability of specific antibody responses in recovered MERS and COVID-19 patients is limited.…”

“…Moreover, the nature of humoral immunity as a form of protective therapy remains unclear [ 8 ]. We previously found that anti-MERS-CoV spike antigen-specific IgG responses, including the neutralizing activity, and the presence of antibody-secreting memory B cells lasted up to three years after infection and were significantly correlated with disease severity [ 7 ]. In addition, sera with high neutralizing antibody titers suppressed viral replication but could not reduce excessive pulmonary inflammation during fatal infection in a transgenic mouse model [ 7 ].…”

“…We previously found that anti-MERS-CoV spike antigen-specific IgG responses, including the neutralizing activity, and the presence of antibody-secreting memory B cells lasted up to three years after infection and were significantly correlated with disease severity [ 7 ]. In addition, sera with high neutralizing antibody titers suppressed viral replication but could not reduce excessive pulmonary inflammation during fatal infection in a transgenic mouse model [ 7 ]. In the present study, we further assessed antibody titers against the MERS-CoV spike antigen in plasma samples collected from recovered Korean MERS patients for five years after the 2015 MERS outbreak and assessed the longevity of spike-specific antibody responses and neutralizing activity in order to determine their half-lives.…”

COVID-19 in a case previously infected with MERS-CoV: No cross immunity

“…It also becoming clear that levels of specific antibody responses and opportunity to recover them in testing is significantly dependent on clinical severity and duration of viral persistence. 8 A recent study showed that anti-SARS-CoV-2 antibodies to the spike protein decreased over 60 days in healthcare personnel with 58% of seropositive individuals becoming seronegative. 9 T-cell studies found reactions to SARS-CoV2 in blood samples from people who had not been exposed to the virus suggesting the possibility of cross-reactivity with other coronaviruses, including common-cold types.…”