Cynomolgus Macaque as an Animal Model for Severe Acute Respiratory Syndrome

Abstract

BackgroundThe emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV.Methods and FindingsIn order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.ConclusionsSARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines

“…Alternatively, the ferrets used in this study were older, and age has been shown to be an important susceptibility factor in the mouse model (Rockx et al, 2007). No other animal, including cynomolgus macaques, has been reported to experience fever, which is the most common sign in human SARS-CoV infection (above 99 %) (Skowronski et al, 2005;Lawler et al, 2006). Thus, ferrets are a good model for SARS-CoV because they are susceptible to infection, support replication in the upper and lower respiratory tracts, develop clinical disease (including fever), shed virus from the upper airway and develop severe lung pathology; this is in agreement with Ferret lungs were analysed on the day of sacrifice and scored for pathology on an increasing scale from normal to multifocal lesions (most severe disease).…”

Cardiothoracic ratio and vertebral heart size (VHS) to standardize the heart size of the tufted capuchin (Cebus apella Linnaeus, 1758) in computerized radiographic images

“…In this context, radiographic images of the primate thorax can help elucidate pathological processes intrinsic to the species and help in the study of disease models, or further, for morphometric studies of interest to primatology (Lawler et al 2006, Sharpe et al 2010, Alves 2012.…”

An immunosuppressed Syrian golden hamster model for SARS-CoV infection

“…Animal models described to date include several inbred mouse strains, hamsters, civet cats, ferrets, cats, or nonhuman primates (Fouchier et al, 2003; Glass et al, 2004; Greenough et al, 2005; Hogan et al, 2004; Lawler et al, 2006; Martina et al, 2003; McAuliffe et al, 2004; Qin et al, 2005; Roberts et al, 2005a; 2005b; 2007; Rowe et al, 2004a; Subbarao et al, 2004; ter Meulen et al, 2004; Wu et al, 2005). The timecourse of virus replication in these small animal models is significantly more rapid than that observed in human infections (Roberts et al, 2008) and no model fully reproduces the clinical illness or the pathology observed in humans.…”