a synthetic consensus anti-spike protein dna vaccine induces protective immunity against middle east respiratory syndrome coronavirus in nonhuman primates.first identified in 2012, middle east respiratory syndrome (mers) is caused by an emerging human coronavirus, which is distinct from the severe acute respiratory syndrome coronavirus (sars-cov), and represents a novel member of the lineage c betacoronoviruses. since its identification, mers coronavirus (mers-cov) has been linked to more than 1372 infections manifesting with severe morbidity and, often, mortality (about 495 deaths) in the arabian peninsula, europe, and, most recently, the united ...026290414
tropism and replication of middle east respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study.middle east respiratory syndrome coronavirus (mers-cov) is a zoonotic infection causing severe viral pneumonia, with index cases having resided in or recently travelled to the arabian peninsula, and is a global concern for public health. limited human-to-human transmission, leading to some case clusters, has been reported. mers-cov has been reported in dromedary camels but phenotypic characterisation of such viruses is limited. we aimed to compare mers-cov isolates from dromedaries in saudi arab ...201425174549
host species restriction of middle east respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4.middle east respiratory syndrome coronavirus (mers-cov) emerged in 2012. recently, the mers-cov receptor dipeptidyl peptidase 4 (dpp4) was identified and the specific interaction of the receptor-binding domain (rbd) of mers-cov spike protein and dpp4 was determined by crystallography. animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for mers-cov. here, we investigated the role of dpp4 in this observed species tropism. cell lines of human and nonhuman ...201424899185
comparative pathology of rhesus macaque and common marmoset animal models with middle east respiratory syndrome coronavirus.middle east respiratory syndrome (mers), which is caused by a newly discovered coronavirus (cov), has recently emerged. it causes severe viral pneumonia and is associated with a high fatality rate. however, the pathogenesis, comparative pathology and inflammatory cell response of rhesus macaques and common marmosets experimentally infected with mers-cov are unknown. we describe the histopathological, immunohistochemical, and ultrastructural findings from rhesus macaque and common marmoset animal ...201728234937
an acute immune response to middle east respiratory syndrome coronavirus replication contributes to viral pathogenicity.middle east respiratory syndrome coronavirus (mers-cov) was first identified in a human with severe pneumonia in 2012. since then, infections have been detected in >1500 individuals, with disease severity ranging from asymptomatic to severe, fatal pneumonia. to elucidate the pathogenesis of this virus and investigate mechanisms underlying disease severity variation in the absence of autopsy data, a rhesus macaque and common marmoset model of mers-cov disease were analyzed. rhesus macaques develo ...201626724387
animal models of middle east respiratory syndrome coronavirus infection.the emergence of the middle east respiratory syndrome coronavirus (mers-cov) in 2012 marked the second time that a new, highly pathogenic coronavirus has emerged in the human population in the 21st century. in this review, we discuss the current state of knowledge of animal models of mers-cov infection. commonly used laboratory animal species such as syrian hamsters, mice and ferrets are not susceptible to mers-cov, due to differences in the mers-cov receptor dipeptidyl peptidase 4 (dpp4). the i ...201526192750
infection with mers-cov causes lethal pneumonia in the common marmoset.the availability of a robust disease model is essential for the development of countermeasures for middle east respiratory syndrome coronavirus (mers-cov). while a rhesus macaque model of mers-cov has been established, the lack of uniform, severe disease in this model complicates the analysis of countermeasure studies. modeling of the interaction between the mers-cov spike glycoprotein and its receptor dipeptidyl peptidase 4 predicted comparable interaction energies in common marmosets and human ...201425144235
a comparative review of animal models of middle east respiratory syndrome coronavirus infection.middle east respiratory syndrome coronavirus (mers-cov) was initially isolated from a saudi arabian man with fatal pneumonia. since the original case in 2012, mers-cov infections have been reported in >1500 humans, and the case fatality rate is currently 35%. this lineage c betacoronavirus has been reported to cause a wide range of disease severity in humans, ranging from asymptomatic to progressive fatal pneumonia that may be accompanied by renal or multiorgan failure. although the clinical pre ...201626869154
middle east respiratory syndrome coronavirus (mers-cov) causes transient lower respiratory tract infection in rhesus 2012, a novel betacoronavirus, designated middle east respiratory syndrome coronavirus or mers-cov and associated with severe respiratory disease in humans, emerged in the arabian peninsula. to date, 108 human cases have been reported, including cases of human-to-human transmission. the availability of an animal disease model is essential for understanding pathogenesis and developing effective countermeasures. upon a combination of intratracheal, ocular, oral, and intranasal inoculation with ...201324062443
[advances in the animal models of mers-cov].the middle east respiratory syndrome coronavirus (mers-cov) was first isolated in 2012 from patients that died from severe pneumonia. it was another coronavirus which resulted in severe infection of humans, apart from the severe acute respiratory syndrome coronavirus. the development of an appropriate animal model is necessary to study the pathogenesis and to evaluate the intervening measures against mers-cov infection. to date, several small animals(e.g., mice, syrian hamsters, and ferrets) hav ...201629963837
a spike-modified middle east respiratory syndrome coronavirus (mers-cov) infectious clone elicits mild respiratory disease in infected rhesus macaques.the recurrence of new human cases of middle east respiratory syndrome coronavirus (mers-cov) underscores the need for effective therapeutic countermeasures. nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. however, mers-cov-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. considering this limitation, we wa ...201830013082
a recombinant vsv-vectored mers-cov vaccine induces neutralizing antibody and t cell responses in rhesus monkeys after single dose immunization.middle east respiratory syndrome coronavirus (mers-cov) has been a highly threatening zoonotic pathogen since its outbreak in 2012. similar to sars-cov, mers-cov belongs to the coronavirus family and can induce severe respiratory symptoms in humans, with an average case fatality rate of 35% according to the world health organization. spike (s) protein of mers-cov is immunogenic and can induce neutralizing antibodies, thus is a potential major target for vaccine development. here we constructed a ...201829246504
treatment with interferon-α2b and ribavirin improves outcome in mers-cov-infected rhesus macaques.the emergence of middle east respiratory syndrome coronavirus (mers-cov) is of global concern: the virus has caused severe respiratory illness, with 111 confirmed cases and 52 deaths at the time of this article's publication. therapeutic interventions have not been evaluated in vivo; thus, patient management relies exclusively on supportive care, which, given the high case-fatality rate, is not highly effective. the rhesus macaque is the only known model organism for mers-cov infection, developi ...201324013700
interferon-β and mycophenolic acid are potent inhibitors of middle east respiratory syndrome coronavirus in cell-based assays.the middle east respiratory syndrome coronavirus (mers-cov) presents a novel emerging threat to public health worldwide. several treatments for infected individuals have been suggested including ifn, ribavirin and passive immunotherapy with convalescent plasma. administration of ifn-α2b and ribavirin has improved outcomes of mers-cov infection in rhesus macaques when administered within 8 h post-challenge. however, detailed and systematic evidence on the activity of other clinically available dr ...201424323636
evaluation of candidate vaccine approaches for mers-cov.the emergence of middle east respiratory syndrome coronavirus (mers-cov) as a cause of severe respiratory disease highlights the need for effective approaches to cov vaccine development. efforts focused solely on the receptor-binding domain (rbd) of the viral spike (s) glycoprotein may not optimize neutralizing antibody (nab) responses. here we show that immunogens based on full-length s dna and s1 subunit protein elicit robust serum-neutralizing activity against several mers-cov strains in mice ...201526218507
recombinant receptor binding domain protein induces partial protective immunity in rhesus macaques against middle east respiratory syndrome coronavirus challenge.development an effective vaccine against middle east respiratory syndrome coronavirus (mers-cov) is urgent and limited information is available on vaccination in nonhuman primate (nhp) model. we herein report of evaluating a recombinant receptor-binding domain (rrbd) protein vaccine in a rhesus macaque model.201526629538
3b11-n, a monoclonal antibody against mers-cov, reduces lung pathology in rhesus monkeys following intratracheal inoculation of mers-cov jordan-n3/2012.middle east respiratory syndrome coronavirus (mers-cov) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the middle east. to date there have been over 1600 laboratory confirmed cases of mers-cov in 26 countries with a case fatality rate of 36%. given the endemic region, it is possible that mers-cov could spread during the annual hajj pilgrimage, necessitating countermeasure development. in this report, we describe the cli ...201626828465
mers-cov virus-like particles produced in insect cells induce specific humoural and cellular imminity in rhesus macaques.middle east respiratory syndrome coronavirus (mers-cov) causes severe respiratory disease in humans with a case fatality rate of over 39%, and poses a considerable threat to public health. a lack of approved vaccine or drugs currently constitutes a roadblock in controlling disease outbreak and spread. in this study, we generated mers-cov vlps using the baculovirus expression system. electron microscopy and immunoelectron microscopy results demonstrate that mers-cov vlps are structurally similar ...201727050368
generation of a transgenic mouse model of middle east respiratory syndrome coronavirus infection and disease.the emergence of middle east respiratory syndrome-coronavirus (mers-cov) in the middle east since 2012 has caused more than 900 human infections with ∼40% mortality to date. animal models are needed for studying pathogenesis and for development of preventive and therapeutic agents against mers-cov infection. nonhuman primates (rhesus macaques and marmosets) are expensive models of limited availability. although a mouse lung infection model has been described using adenovirus vectors expressing h ...201525589660
a single dose of chadox1 mers provides protective immunity in rhesus macaques.developing a vaccine to protect against the lethal effects of the many strains of coronavirus is critical given the current global pandemic. for middle east respiratory syndrome coronavirus (mers-cov), we show that rhesus macaques seroconverted rapidly after a single intramuscular vaccination with chadox1 mers. the vaccine protected against respiratory injury and pneumonia and reduced viral load in lung tissue by several orders of magnitude. mers-cov replication in type i and ii pneumocytes of c ...202032577525
clinical benefit of remdesivir in rhesus macaques infected with sars-cov-2.effective therapies to treat coronavirus disease 2019 (covid-19) are urgently needed. while many investigational, approved, and repurposed drugs have been suggested as potential treatments, preclinical data from animal models can guide the search for effective treatments by ruling out those that lack efficacy in vivo. remdesivir (gs-5734) is a nucleotide analogue prodrug with broad antiviral activity1,2 that is currently being investigated in covid-19 clinical trials and recently received emerge ...202032516797
importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on mers-cov spike to avoid neutralization escape.middle east respiratory syndrome coronavirus (mers-cov) causes a highly lethal pulmonary infection with ∼35% mortality. the potential for a future pandemic originating from animal reservoirs or healthcare-associated events is a major public health concern. there are no vaccines or therapeutic agents currently available for mers-cov. using a probe-based single b cell-cloning strategy, we have identified and characterized multiple neutralizing mabs specifically binding to the receptor binding doma ...201829514901
pathogenicity and viral shedding of mers-cov in immunocompromised rhesus macaques.middle east respiratory syndrome coronavirus (mers-cov) has recently emerged in the middle east. since 2012, there have been approximately 2,100 confirmed cases, with a 35% case fatality rate. disease severity has been linked to patient health status, as people with chronic diseases or an immunocompromised status fare worse, although the mechanisms of disease have yet to be elucidated. we used the rhesus macaque model of mild mers to investigate whether the immune response plays a role in the pa ...201829483914
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