Emergence and spread of neutralization-escaping MERS-CoV during 2015 Korea outbreak and antibody responses in the recovered patients
Year: 2023
Type: dissertation
Abstract: The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several "superspreading" events.It has been reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak.To assess the potential association of spike mutations with superspreading events, I collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology.Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections.Given the lack of specific antiviral therapies, the application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridge this gap.I have traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea and 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.Anti-spike-specific IgG responses, including neutralizing activity and antibodysecreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia.In general, antibody titers gradually decreased annually by less than 2-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 a high neutralizing titer (>1/5000).However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss.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.
Author: 아이마
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7056040848