SARS vaccines: where are we?

Rachel L. Roper; Kristina E. Rehm

Disclosures

Expert Rev Vaccines. 2009;8(7):887-898. 

In This Article

Animal Models

Animal models developed for SARS include macaques,[3,109] African green monkey,[64,110] ferrets,[9] mice[111,112] and hamsters,[113] and the Chinese masked palm civet.[114] An excellent review of animal models was recently released,[115] and we will focus here on some of the newer developments, especially in ferrets.

Mouse models are of questionable use for efficacy studies as they do not reproduce the clinical signs or severe disease of SARS in humans,[111,112] unless immunodeficient or aged mice are used.[116] However, the model has been improved by the use of mouse-adapted SARS and human ACE2 transgenic mice, although both models still have significant caveats.[115,117,118,119] Hamsters also do not exhibit clinical signs of SARS-CoV infection. Ferrets have been used widely for the study of influenza and are susceptible to SARS-CoV infection, with lung pathology and virus shedding.[9,120] One ferret study indicated that upon intranasal administration of SARS-CoV Toronto 2 strain, no clinical signs were observed, although viral RNA could be detected in pharyngeal swabs.[63,121] However, several other studies showed the ferret to be one of the better models for the display of clinical signs, viral replication and lung pathology,[51] reflecting SARS pathogenesis in humans.[122]

In the most recently reported ferret study,[52] SARS-CoV challenge resulted in ferrets with clinical signs of infection (elevated temperature, nasal discharge and sneezing). No other animal, including cynomolgus macaques, has been reported to regularly experience fever, which is the most common sign in human SARS-CoV infection, (>99%).[123,124] Thus, ferrets are a good model for SARS-CoV because they support replication in the upper and lower respiratory tracts, develop clinical disease, shed virus from the upper airway and develop severe lung pathology. Ferrets are also outbred, allowing the assessment of a range of individual responses that are documented in human SARS. Finally, the ferret model is a nonrodent model and is significantly less expensive and difficult to study than nonhuman primates. The main disadvantages of this model are that the ferret immune system is not well defined, there is a dearth of reagents and, as they are outbred, larger numbers are needed to assess statistical significance.

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