Challenge infection model for MERS-CoV based on naturally infected camels

Abstract

Background: Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging virus that infects humans and camels with no approved antiviral therapy or vaccine. Some vaccines are in development for camels as a one-health intervention where vaccinating camels is proposed to reduce human viral exposure. This intervention will require an understanding of the prior exposure of camels to the virus and appropriate vaccine efficacy studies in camels. Methods: We conducted a cross sectional seroprevalence study in young dromedary camels to determine the rate of MERS-CoV seropositivity in young camels. Next, we utilised naturally infected camels as a natural challenge model that can be used by co-housing these camels with healthy naive camels in a ratio of 1 to 2. This model is aimed to support studies on natural virus transmission as well as evaluating drug and vaccine efficacy. Results: We found that 90% of the screened camels have pre-existing antibodies for MERS-CoV. In addition, the challenge model resulted in MERS-CoV transmission within 48 h with infections that continued for 14 days post challenge. Conclusions: Our finding suggests that the majority of young dromedary camels in Saudi Arabia are seropositive and that naturally infected camels can serve as a challenge model to assess transmission, therapeutics, and vaccine efficacy.

High Rate of Circulating MERS-CoV in Dromedary Camels at Slaughterhouses in Riyadh, 2019

“…Most of the slaughtering process and meat preparation are done with semi-automation handling of the animals and in areas with restricted authorized access; yet, this high rate of viral infection in camels is worrisome.The study showed an overall high seropositivity of MERS-CoV in camel serum samples (70.81%), which is consistent with previous studies that reported high prevalence of MERS-CoV antibodies in camels, ranging from 74% to 100%, in multiple African and Arabian countries(13,22,(30)(31)(32)(33). Infected camels in this study had pre-existing MERS-CoV antibodies, which further confirm previous data of MERS-CoV re-infection in camels(17,22,25). Some of which studies MERS-CoV seroprevalence in young camels; showing that MERS-CoV antibodies were found in > 96% of calves above 2 years of age and 80% of calves below 1 year of age in Dubai ,UAE (9).…”

“…Arabia reports by far the most MERS cases. The country has a large population of dromedary camels, yet it is lower than that of astern Africa (22). Although camels are the confirmed direct zoonotic source of the infection, several gaps in knowledge remains unaddressed, such as the mechanism of virus transmission from camels to humans, the low infection rate in camel workers, the potential infectiousness of asymptomatic cases, and the rate of virus circulation in camels every year.…”

“…Riyadh was selected as a highly populated city as well as having a large population of camels (22). Therefore, this study assesses the presence of MERS-CoV, the genetic sequences of the spike gene, and anti-MERS-CoV neutralizing antibodies in this population of dromedary camels.…”

Recent Advances in Camel Immunology

“…The very high seroprevalence rates (74–100%) of MERS-CoV in camel populations in Africa and the Arabian Peninsula indicate high infection and transmission rates of the virus in camels ( 16 ). The dipeptidyl peptidase 4 (DPP4; CD26), a type II transmembrane glycoprotein involved in cleavage of dipeptides and degradation of incretins ( 229 ), has been identified as a functional receptor for the MERS-CoV ( 230 – 232 ).…”

“…The characterization of camel NK and cytotoxic T cells and their role in anti-viral immunity in the context of infection with MERS-CoV is one of the promising lines of research. MERS-CoV naturally infected camels are currently discussed as a challenge model in vaccine efficacy studies ( 16 ). The characterization of mucosal immune mechanisms in the camel respiratory tract, including detailed phenotypic and functional analyses of immune cells in bronchoalveolar lavages and lung parenchymas of MERS-CoV-infected and recovered camels would be a prerequisite for the elucidation of MERS-CoV pathogenesis in these animals.…”