Neutralizing Monoclonal Antibodies as Promising Therapeutics against Middle East Respiratory Syndrome Coronavirus Infection

Since emerging in 2012, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has been a global public health threat with a high fatality rate and worldwide distribution. There are no approved vaccines or therapies for MERS until now. Passive immunotherapy with neutralizing monoclonal antibodies (mAbs) is an effective prophylactic and therapeutic reagent against emerging viruses. In this article, we review current advances in neutralizing mAbs against MERS-CoV. The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. A major problem with neutralizing mAb therapy is mutant escape under selective pressure, which can be solved by combination of neutralizing mAbs targeting different epitopes. Neutralizing mAbs are currently under preclinical evaluation, and they are promising candidate therapeutic agents against MERS-CoV infection.

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Passive Immunotherapy with Dromedary Immune Serum in an Experimental Animal Model for Middle East Respiratory Syndrome Coronavirus Infection

Journal of Virology ◽

10.1128/jvi.00446-15 ◽

2015 ◽

Vol 89 (11) ◽

pp. 6117-6120 ◽

Cited By ~ 43

Author(s):

Jincun Zhao ◽

Ranawaka A. P. M. Perera ◽

Ghazi Kayali ◽

David Meyerholz ◽

Stanley Perlman ◽

...

Keyword(s):

Middle East ◽

Pulmonary Infection ◽

Serum Antibody ◽

Case Fatality ◽

Immune Serum ◽

Middle East Respiratory Syndrome ◽

Specific Therapy ◽

Passive Immunotherapy ◽

Coronavirus Infection ◽

Kinetics Of

ABSTRACTMiddle East respiratory syndrome (MERS) is a highly lethal pulmonary infection. Serum from convalescent MERS patients may provide some benefit but is not readily available. In contrast, nearly all camels in the Middle East have been infected with MERS-CoV. Here, we show that sera obtained from MERS-immune camels augment the kinetics of MERS-CoV clearance and reduce the severity of pathological changes in infected lungs, with efficacy proportional to the titer of MERS-CoV-neutralizing serum antibody.IMPORTANCEMiddle East respiratory syndrome, caused by a coronavirus, is highly lethal, with a case fatality rate of 35 to 40%. No specific therapy is available, and care is generally supportive. One promising approach is passive administration of sera from convalescent human MERS patients or other animals to exposed or infected patients. The vast majority of, if not all, camels in the Middle East have been infected with MERS-CoV, and some contain high titers of antibody to the virus. Here, we show that this antibody is protective if delivered either prophylactically or therapeutically to mice infected with MERS-CoV, indicating that this may be a useful intervention in infected patients.

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Lack of serological evidence of Middle East respiratory syndrome coronavirus infection in virus exposed camel abattoir workers in Nigeria, 2016

Eurosurveillance ◽

10.2807/1560-7917.es.2018.23.32.1800175 ◽

2018 ◽

Vol 23 (32) ◽

Cited By ~ 12

Author(s):

Ray TY So ◽

Ranawaka APM Perera ◽

Jamiu O Oladipo ◽

Daniel KW Chu ◽

Sulyman A Kuranga ◽

...

Keyword(s):

Middle East ◽

Middle East Respiratory Syndrome ◽

Health Concern ◽

Global Public Health ◽

Zoonotic Infection ◽

Dromedary Camels ◽

Rna Detection ◽

Nasal Swabs ◽

Coronavirus Infection ◽

Abattoir Workers

Background Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic threat of global public health concern and dromedary camels are the source of zoonotic infection. Although MERS-CoV is enzootic in dromedaries in Africa as well as the Middle East, zoonotic disease has not been reported in Africa. Methods: In an abattoir in Kano, Nigeria, we tested nasal swabs from camels and investigated 261 humans with repeated occupational exposure to camels, many of whom also reported drinking fresh camel milk (n = 138) or urine (n = 94) or using camel urine for medicinal purposes (n = 96). Results: Weekly MERS-CoV RNA detection in January–February 2016 ranged from 0–8.4% of camels sampled. None of the abattoir workers with exposure to camels had evidence of neutralising antibody to MERS-CoV. Conclusion: There is a need for more studies to investigate whether or not zoonotic transmission of MERS-CoV does take place in Africa.

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Passive immunotherapy for Middle East Respiratory Syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model

Antiviral Research ◽

10.1016/j.antiviral.2016.11.016 ◽

2017 ◽

Vol 137 ◽

pp. 125-130 ◽

Cited By ~ 9

Author(s):

Yongkun Zhao ◽

Chong Wang ◽

Boning Qiu ◽

Chufang Li ◽

Hualei Wang ◽

...

Keyword(s):

Middle East ◽

Mouse Model ◽

Middle East Respiratory Syndrome ◽

Passive Immunotherapy ◽

Coronavirus Infection

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Diagnostic delays in 537 symptomatic cases of Middle East respiratory syndrome coronavirus infection in Saudi Arabia

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2017.07.008 ◽

2017 ◽

Vol 62 ◽

pp. 47-51 ◽

Cited By ~ 15

Author(s):

Anwar E. Ahmed

Keyword(s):

Saudi Arabia ◽

Middle East ◽

Middle East Respiratory Syndrome ◽

Coronavirus Infection ◽

Diagnostic Delays

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Prevalence of diabetes in the 2009 influenza A (H1N1) and the Middle East respiratory syndrome coronavirus: a systematic review and meta-analysis

Journal of Public Health Research ◽

10.4081/jphr.2016.733 ◽

2016 ◽

Vol 5 (3) ◽

Cited By ~ 22

Author(s):

Alaa Badawi ◽

Sueng Gwan Ryoo

Keyword(s):

Systematic Review ◽

Middle East ◽

Influenza A ◽

Meta Analysis ◽

Middle East Respiratory Syndrome ◽

Global Public Health ◽

Epidemiologic Evidence ◽

Severe Acute Respiratory Infection ◽

Influenza A H1n1 ◽

Prevalence Of Obesity

Over the past two decades a number of severe acute respiratory infection outbreaks such as the 2009 influenza A (H1N1) and the Middle East respiratory syndrome coronavirus (MERS-CoV) have emerged and presented a considerable global public health threat. Epidemiologic evidence suggests that diabetic subjects are more susceptible to these conditions. However, the prevalence of diabetes in H1N1 and MERS-CoV has not been systematically described. The aim of this study is to conduct a systematic review and meta-analysis of published reports documenting the prevalence of diabetes in H1N1 and MERS-CoV and compare its frequency in the two viral conditions. Meta-analysis for the proportions of subjects with diabetes was carried out in 29 studies for H1N1 (n=92,948) and 9 for MERS-CoV (n=308). Average age of H1N1 patients (36.2±6.0 years) was significantly younger than that of subjects with MERS-CoV (54.3±7.4 years, P<0.05). Compared to MERS-CoV patients, subjects with H1N1 exhibited 3-fold lower frequency of cardiovascular diseases and 2- and 4-fold higher prevalence of obesity and immunosuppression, respectively. The overall prevalence of diabetes in H1N1 was 14.6% (95% CI: 12.3- 17.0%; P<0.001), a 3.6-fold lower than in MERS-CoV (54.4%; 95% CI: 29.4-79.5; P<0.001). The prevalence of diabetes among H1N1 cases from Asia and North America was ~two-fold higher than those from South America and Europe. The prevalence of diabetes in MERS-CoV cases is higher than in H1N1. Regional comparisons suggest that an etiologic role of diabetes in MERS-CoV may exist distinctive from that in H1N1.

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