Animal Models
Guinea pigs and nonhuman primates represent the primary animal models for vaccine development because the progression and pathogenesis most closely resemble those of the human disease. Notably, in all cases, there is a conserved tropism for mononuclear phagocytic cells, pathological changes to the liver and spleen, high levels of viremia and high mortality. While symptoms and time course of disease in guinea pigs parallel those in humans, nonhuman primate infection is considered the most predictive and useful for vaccine development.
A murine model was later developed by serial passage of the virus. Though the model allows the use of knockout and inbred strains to evaluate genetic determinants of disease it is considered less predictive of human disease because it relies on a serially passaged, attenuated virus. The mouse-adapted strain seems to have reduced virulence in non-human primates, but is virulent in guinea pigs.
Lymphocyte apoptosis was not reported to be a main feature of ZEBOV infection in mice or guinea pigs, but was a consistent feature of disease in humans4 and non-human primates. Coagulopathy—in particular, haemorrhage and fibrin deposition—is not a main feature of disease caused by the guinea pig or mouse-adapted strains. This pathological feature is not consistently observed in primates and the occurrence in humans has not been well investigated because of the difficulty in obtaining samples.
Thus the differences in pathology between model systems must be considered when planning vaccine studies, as should the observation that it is apparently harder to protect non-human primates than either species of rodent.
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This page last updated: 14 April 2004.
