Immunotherapeutic Efficacy of IgY Antibodies Targeting the Full-Length Spike Protein in an Animal Model of Middle East Respiratory Syndrome Coronavirus Infection.

Sherif A El-Kafrawy,Noriyo Nagata,Esam I Azhar,Aymn T Abbas,Ahmed M Hassan,Sayed S Sohrab,Ashraf A Tabll,Naoko Iwata-Yoshikawa

doi:10.3390/ph14060511

Abstract

Identified in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often fatal acute respiratory illness in humans. No approved prophylactic or therapeutic interventions are currently available. In this study, we developed chicken egg yolk antibodies (IgY Abs) specific to the MERS-CoV spike (S) protein and evaluated their neutralizing efficiency against MERS-CoV infection. S-specific IgY Abs were produced by injecting chickens with the purified recombinant S protein of MERS-CoV at a high titer (4.4 mg/mL per egg yolk) at week 7 post immunization. Western blotting and immune-dot blot assays demonstrated specific binding to the MERS-CoV S protein. In vitro neutralization of the generated IgY Abs against MERS-CoV was evaluated and showed a 50% neutralizing concentration of 51.42 μg/mL. In vivo testing using a human-transgenic mouse model showed a reduction of viral antigen positive cells in treated mice, compared to the adjuvant-only controls. Moreover, the lung cells of the treated mice showed significantly reduced inflammation, compared to the controls. Our results show efficient neutralization of MERS-CoV infection both in vitro and in vivo using S-specific IgY Abs. Clinical trials are needed to evaluate the efficiency of the IgY Abs in camels and humans.

Highlights

IntroductionRespiratory infections affect millions of people worldwide and pose risks to many, especially children and the elderly [1]
These results suggest that anti-S MERS-CoV Immunoglobulin Y (IgY) antibodies exexhibited potentability abilitytotoneutralize neutralizeMERS-CoV
The results presented in this study provide evidence for the specific and efficient neutralization of MERS-CoV using anti-S IgY antibodies in vitro and in an animal model of MERS-CoV

Summary

Introduction

Respiratory infections affect millions of people worldwide and pose risks to many, especially children and the elderly [1]. Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic virus causing severe and often fatal respiratory illness in humans [2]. MERS-CoV was first detected in 2012 [3,4]. Since documented infections in humans have steadily increased, with 2566 cases as of December 2020 and an estimated 35% fatality rate [5]. The virus can transmit from camel to camel, and dromedary camels demonstrate high seropositivity to MERS-CoV [6,7,8]. Transmission from camel to human occurs, and several risk factors, such as direct contact with infected dromedary

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