Animal Models Used in Vaccine development:
Unfortunately, adequate animal models for assessing Coronaviruses vaccines are not available easily rendering the vaccine production cycle really difficult. Succeeding in developing an appropriate animal model which could imitate the clinical condition in humans would be an effective tool to explore the pathophysiology of the disease and help to evaluate the suitable vaccines and treatments with the minor possible harmful effects. In fact, different types of animals have been used to assess SARS, MERS and SARS-CoV-2 infections. Examples of these animals are mice, guinea pigs, hamsters, rabbits and rhesus macaques (93).
Several attempts were done to develop suitable animal models for SARS-CoV, however, the specificity of the virus to ACE2 was a significant obstacle. Then, Yang et al., succeeded in developing an appropriate transgenic mouse model through the introduction of hACE2 gene into the mouse genome(94). As for MERS, the initial animal model used for development of its vaccine was rhesus macaques. The animal models showed clinical symptoms similar to those occurring in humans such as pyrexia, cough and decreased appetite(95). In addition, other animal models were used for MERS including the common marmoset where the clinical condition progressed to fatal pneumonia. Fortunately, antibodies production as well as activated cell mediated immune response could be identified in these animals after exposure to MERS vaccine (96). Furthermore, golden Syrian hamster was used as animal model to evaluate the vaccine development process against several strains of SARS to assess the virus pathophysiology as well as the vaccine effectiveness and safety(97).
Incapability of MERS to replicate in the lungs of mice, hamsters or ferrets made these animals inapplicable animal models for it. These animals are naturally susceptible to SARS but resist MERS infection. However, Zhou et al., have been succeeded in modifying them genetically to be able for MERS infection and replication(98). Such efforts for genetic modification of these small animals including mice and rabbits to enable them to be susceptible to such viral infections, though time consuming, but are favored as these models are more cost-effective and easier to be manipulated when compared with larger animals (99). More studies are required in order to identify the most appropriate animal models for the novel SARS-CoV-2. This will involve determining the degree of specificity of the virus to its receptors on host cells as well as investigating its pathophysiology and specific immune response.