Doubtless the simple answer is that these animals differ, and that the amino acids of their ACE2 receptors differ. Are there other reasons?

Chan, working with his HKU colleague, microbiologist Kwok-Yung Yuen, and others, pinpointed the problem by doing a cross-species comparison of the segment of ACE2 to which SARS-CoV-2 first attaches. In the mouse, 11 of 29 amino acids of this critical domain differed from the human version. (Rats had 13 differences, but hamsters only had four.)

I quote p 738 of Y. W. Kam et al. Vaccine 25, 729–740; 2007.

      Vaccine-mediated protection against SARS-CoV infection in mice has been demonstrated using different vaccine approaches [19,20,65]. However, mice do not replicate SARS-CoV to high titers and do not showpronounced pathology in lungs [15]. On the contrary, ferrets [28], cynomolgus macaques [29] and hamsters [30] have been shown to support high titer replication of SARS-CoV in the respiratory tract associated with pneumonitis. In order to assess the respective role of neutralization or ADE in vivo we performed SARSCoVchallenge experiments in hamsters vaccinated with three doses of 2, 10 or 50 g of protein in alum adjuvant. All vaccinated groups showed a significant decrease of viral load at 3 days post challenge by at least four orders of magnitude without signs of enhanced lung pathology. The rare foci of hepatocyte necrosis that we observed in these hamsters did not correlate with pre-challenge neutralizing antibody titers, liver enzyme levels (pre- or post-challenge), or immunohistochemical detection of SARS-CoV antigen suggesting that hepatic cellular necrosis is unrelated to SARS-CoV immunization or infection in Syrian golden hamsters. This contrasts with a report of hepatitis 28 days following challenge with SARS-CoV in ferrets vaccinated with a poorly immunogenic recombinantMVAvaccine expressing SARS-CoV spike protein [24].

Why will it take so long to develop a COVID-19 vaccine? - The Globe and Mail

Another study revealed that some investigational SARS vaccines produced negative side effects in some types of animals (such as ferrets) but not in others (such as mice). For that reason, many researchers are convinced that a vaccine should be tested in two different types of animals, Kozak says.


One big reason for the difference is how close the vaccine's epitopes match the natural epitopes in the animals. When they are similar an attempted immune response to the vaccine will either tend to give an autoimmune response; or no response as the relevant immune cells were destroyed during maturation (to prevent autoimmune diseases).

The reports of autoimmune disease from SARS-Cov-2 (kawasaki disease) would seem to reduce the targets for a successful vaccine.

Sorry no refs on this.

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