Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

Uyeki, Timothy M.; Erlandson, Karl J.; Korch, George W.; O’Hara, Michael; Wathen, Michael W.; Hu-Primmer, Jean; Hojvat, Sally; Stemmy, Erik J.; Donabedian, Armen M.

doi:10.3201/eid2207.160022

Cited by 17 publications

(20 citation statements)

References 66 publications

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“…There are currently no approved vaccines or treatments for MERS-CoV, however both vaccine and drug candidates have been shown to be effective in vitro and/or in in vivo animal models [2,3]. The S protein of MERS-CoV is a prime target for vaccination strategies because it is the main attachment factor and is expressed on the virion surface.…”

Section: Mers-covmentioning

confidence: 99%

MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

Coleman

Venkataraman

Liu

et al. 2017

Vaccine

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The Middle East respiratory syndrome coronavirus (MERS-CoV) was first discovered in late 2012 and has gone on to cause over 1800 infections and 650 deaths. There are currently no approved therapeutics or vaccinations for MERS-CoV. The MERS-CoV spike (S) protein is responsible for receptor binding and virion entry to cells, is immunodominant and induces neutralizing antibodies in vivo, all of which, make the S protein an ideal target for anti-MERS-CoV vaccines. In this study, we demonstrate protection induced by vaccination with a recombinant MERS-CoV S nanoparticle vaccine and Matrix-M1 adjuvant combination in mice. The MERS-CoV S nanoparticle vaccine produced high titer anti-S neutralizing antibody and protected mice from MERS-CoV infection in vivo.

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Section: Mers-covmentioning

confidence: 99%

MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

Coleman

Venkataraman

Liu

et al. 2017

Vaccine

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“…MERS-CoV poses a significant threat to public health worldwide because of the high fatality rate of MERS infection and potential outbreaks of MERS-CoV infection in healthcare facilities. Furthermore, there are no specific vaccines or therapeutics for the prevention or treatment of MERS-CoV infection [15][16][17][18][19][20][21].…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

A novel luciferase immunosorbent assay performs better than a commercial enzyme-linked immunosorbent assay to detect MERS-CoV specific IgG in humans and animals

Wang¹,

Wang²,

Deng³

et al. 2019

Biosafety and Health

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The Middle East respiratory syndrome (MERS) is a lethal zoonosis caused by MERS coronavirus (MERS-CoV) and poses a significant threat to public health worldwide. Therefore, a rapid, sensitive, and specific serologic test for detecting anti-MERS-CoV antibodies in both humans and animals is urgently needed for the successful management of this illness. Here, we evaluated various novel luciferase immunosorbent assays (LISA) based on nucleocapsid protein (NP) as well as fragments derived from spike protein (S) including subunit 1 (S1), N terminal domain (NTD), receptorbinding domain (RBD) and subunit 2 (S2) of S for the detection of MERS-CoV-specific IgG. Fusion proteins, including nanoluciferase (NLuc) and various fragments derived from the NP or S protein of MERS-CoV, were expressed in human embryonic kidney 293 T cells. LISAs that detected anti-MERS-CoV IgG were further developed using cell lysates expressing various fusion proteins. Panels of human or animal samples infected with MERS-CoV were used to analyze the sensitivity and specificity of various LISAs in reference to a MERS-CoV RT-PCR, commercial S1-based ELISA, and pseudovirus particle neutralization test (ppNT). Our results showed that the S1-, RBD-, and NP-LISAs were more sensitive than the NTD-and S2-LISAs for the detection of anti-MERS-CoV IgG. Furthermore, the S1-, RBD-, and NP-LISAs were more sensitive (by at least 16-fold) than the commercially available S1-ELISA. Moreover, the S1-, RBD-, and NP-LISA specifically recognized anti-MERS-CoV IgG and did not cross-react with samples derived from other human CoV (OC43, 229E, HKU1, NL63)-infected patients. More importantly, these LISAs proved their applicability and reliability for detecting anti-MERS-CoV IgG in samples from camels, monkeys, and mice, among which the RBD-LISA exhibited excellent performance. The results of this study suggest that the novel MERS-CoV RBD-and S1-LISAs are highly effective platforms for the rapid and sensitive detection of anti-MERS-CoV IgG in human and animal samples. These assays have the potential to be used as serologic tests for the management and control of MERS-CoV infection.

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“…Biological assay standardization is critical. 2,10,17,71,72 At a minimum, the development of relevant biological assays with adequate sensitivity and specificity for the application should use biostatistics to establish and verify assay performance and to maintain the ability to produce stable and reproducible results over time to support diagnostic or vaccine program needs. The criteria for acceptability of any given test system will be dependent upon the nature of the pathogen, our understanding of the immunology to fight the pathogen (both of which may be poorly understood in an EID situation) and the assay platform.…”

Section: Future Preparedness For Eidsmentioning

confidence: 99%

Emerging infectious disease laboratory and diagnostic preparedness to accelerate vaccine development

Roberts¹

2019

Human Vaccines & Immunotherapeutics

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Rapid vaccine development in response to an outbreak of a new emerging infectious disease (EID) is a goal targeted by public health agencies worldwide. This goal becomes more complicated when there are no standardized sets of viral and immunological assays, no accepted and well-characterized samples, standards or reagents, and no approved diagnostic tests for the EID pathogen. The diagnosis of infections is of critical importance to public health, but also in vaccine development in order to track incident infections during clinical trials, to differentiate natural infection responses from those that are vaccine-related and, if called for by study design, to exclude subjects with prior exposure from vaccine efficacy trials. Here we review emerging infectious disease biological standards development, vaccine clinical assay development and trial execution with the recent experiences of MERS-CoV and Zika virus as examples. There is great need to establish, in advance, the standardized reagents, sample panels, controls, and assays to support the rapid advancement of vaccine development efforts in response to EID outbreaks.

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Development of Medical Countermeasures to Middle East Respiratory Syndrome Coronavirus

Cited by 17 publications

References 66 publications

MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

MERS-CoV spike nanoparticles protect mice from MERS-CoV infection

A novel luciferase immunosorbent assay performs better than a commercial enzyme-linked immunosorbent assay to detect MERS-CoV specific IgG in humans and animals

Emerging infectious disease laboratory and diagnostic preparedness to accelerate vaccine development

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