Asymptomatic Middle East Respiratory Syndrome Coronavirus Infection in Rabbits

Haagmans, Bart L.; Brand, Judith M. A. van den; Provacia, Lisette B.; Raj, V. Stalin; Stittelaar, Koert J.; Getu, Sarah; Waal, Leon de; Bestebroer, Theo M.; Amerongen, Geert van; Verjans, Georges M. G. M.; Fouchier, Ron A. M.; Smits, Saskia L.; Kuiken, Thijs; Osterhaus, Albert D. M. E.

doi:10.1128/jvi.00661-15

Cited by 75 publications

(96 citation statements)

References 16 publications

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“…However, the virus does not infect most small experimental animals such as mice, ferrets, rats, and hamsters, mainly because of the different DPP4 in these animals therefore posing a challenge for developing a vaccine by delaying scientific investigation on the virus infection, pathogenicity, and transmission. A rabbit model was reported to support MERS‐CoV, but more small animal models were required to accelerate MERS‐CoV research; therefore, susceptible mouse models were developed by different methods. The first model was developed by transducing mice with adenoviral vector encoding human DPP4 (AdV‐hDPP4) delivered intranasally to enable mouse cells in the respiratory tract to express hDPP4, allowing viral entry and infection .…”

Section: Animal Models For Vaccine Evaluationmentioning

confidence: 99%

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

Alharbi

2016

Reviews in Medical Virology

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Middle East respiratory syndrome coronavirus (MERS-CoV) is caused by a novel betacoronavirus that was isolated in late 2012 in Saudi Arabia. The viral infections have been reported in more than 1700 humans, ranging from asymptomatic or mild cases to severe pneumonia with a mortality rate of 40%. It is well documented now that dromedary camels contract the infection and shed the virus without notable symptoms, and such animals had been infected by at least the early 1980s. The mechanism of camel to human transmission is still not clear, but several primary cases have been associated with camel contact. There is no approved antiviral drug or vaccine against MERS-CoV despite the active research in this area. Vaccine candidates have been developed using various platforms and regimens and have been tested in several animal models. Here, this article reviews the published studies on MERS-CoV vaccines with more focus on vaccines tested in large animals, including camels. It is foreseeable that the 1-health approach could be the best way of tackling the MERS-CoV endemic in the Arabian Peninsula, by using the mass vaccination of camels in the affected areas to block camel to human transmission. Camel vaccines can be developed in a faster time with fewer regulations and lower costs and could clear this virus from the Arabian Peninsula if accompanied by efficient public health measures.

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Section: Animal Models For Vaccine Evaluationmentioning

confidence: 99%

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

Alharbi

2016

Reviews in Medical Virology

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“…30 Clinical signs and gross lesions were not observed in rabbits inoculated through intratracheal and intranasal routes. Microscopically, lesions were detected in the upper and lower respiratory tract at 3 and 4 days postinoculation (dpi).…”

Section: Rabbitsmentioning

confidence: 99%

“…1, 2), 30 Stanley Perlman, David Meyerholz, and Jincun Zhao (Figs. 3-6), 80 Chien-Te Tseng and Xinrong Tao (Figs.…”

Section: Acknowledgementsmentioning

confidence: 99%

A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection

2016

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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 presentation of human MERS-CoV infection has been documented, many facets of this emerging disease are still unknown and could be studied with animal models. Several animal models of MERS-CoV have been developed, including New Zealand white rabbits, transduced or transgenic mice that express human dipeptidyl peptidase 4, rhesus macaques, and common marmosets. This review provides an overview of the current state of knowledge on human MERS-CoV infections, the probable origin of MERS-CoV, and the available animal models of MERS-CoV infection. Evaluation of the benefits and limitations of these models will aid in appropriate model selection for studying viral pathogenesis and transmission, as well as for testing vaccines and antivirals against MERS-CoV.Keywords animal models, common marmosets, dipeptidyl peptidase 4, mice, Middle East respiratory syndrome coronavirus, pathogenicity, rabbits, respiratory system, review, rhesus macaques, transgenic Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated from a man in Saudi Arabia in 2012, and MERS-CoV infections have now been reported in >20 countries. 76,79 Originally called human coronavirus-EMC/2012, the virus was renamed MERS-CoV by the International Committee on Taxonomy of Viruses. 20,67 In humans, MERS-CoV is 1 of 6 coronaviruses that cause respiratory disease; however, it is currently the only known pathogenic human lineage C betacoronavirus. 31,68 MERS-CoV infections in humans range from asymptomatic to progressive fatal pneumonia with occasional renal or multiorgan failure. 44,52 To date, published autopsy data from fatal human cases are not available, and the exact route of viral transmission to and among humans is unknown. Additionally, there are currently no approved MERS-CoV-specific countermeasures. Thus, development of animal models to study the pathology and pathogenesis of MERS-CoV, the routes of viral transmission, and the efficacy of treatments and vaccines is critical. Here, we review the current state of knowledge on MERS-CoV infections in humans and potential animal reservoirs for the virus and provide an overview and analysis of animal models of MERS-CoV infection.

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“…It can be argued that neither the rabbit nor the mouse model have a high predictive value for potential MERS therapies in humans. Rabbits remain asymptomatic upon inoculation with MERS-CoV and infection appears to be more prominent in the upper respiratory tract, which suggests that disease progression in rabbits differs considerably from that observed in patients who will require antiviral therapy most (Haagmans et al, 2015). The mouse as a model is valuable as an initial validation method of a therapy, but the predictive value of mouse models for therapeutic applications in humans is relatively limited as opposed to non-human primate models (Seok et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets

et al. 2017

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Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Passive immunotherapy via either convalescent plasma or mAbs has proven to be effective for other infectious agents. Following infection with MERS-CoV, common marmosets were treated with high titer hyperimmune plasma or the mAb m336, at 6 and 48 h post inoculation. Both treatments reduced signs of clinical disease, but reduction in viral loads in the respiratory tract were only found in the hyperimmune plasma group. A decrease in gross pathology was found only in the mAb-treated group, but no histological differences were observed between treated and control animals. While both hyperimmune plasma and the m336 treatments reduced the severity of disease in the common marmoset, neither treatment resulted in full protection against disease.

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Asymptomatic Middle East Respiratory Syndrome Coronavirus Infection in Rabbits

Cited by 75 publications

References 16 publications

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

Vaccines against Middle East respiratory syndrome coronavirus for humans and camels

A Comparative Review of Animal Models of Middle East Respiratory Syndrome Coronavirus Infection

Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets

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