Hamster Model of Severe COVID-19 Demonstrates Differential Efficacy of first Licensed Western Vaccines in the Absence of Immunopathogenesis

To combat the COVID-19 pandemic, vaccines have been developed, tested and approved in less than one year. Four vaccines using two technology platforms were authorized early in Europe and the US. Comirnaty and Spikevax are mRNA-based, whereas Jcovden and Vaxzevria utilize adenoviral vectors (AdV). We already described a hamster model of severe COVID-19, in which vaccine-associated immunopathogenesis can be induced by Alum-adjuvanted Spike protein. Such animals were vaccinated here with the early authorized vaccines, challenged, and examined for immunopathogenesis in comparison to Alum+S-vaccinated or naïve hamster after challenge. All vaccinated hamsters produced antibodies binding (bAb) to SARS-CoV-2 Spike, while neutralizing antibodies (nAb) were induced only by the authorized vaccines. Among those, uniform induction of nAbs by mRNA vaccines needed a second dose. Using AdV-based vaccines, nAbs were mostly abundant after just one vaccination, but boostability was low. Upon challenge, Alum+S immunized animals were not protected and developed VAERD. In contrast, all authorized vaccines protected from severe disease, but transient initial weight loss was observed. In accordance with lower nAb titers, a tendency for higher weight loss became evident with Vaxzevria. Histopathology revealed less tissue damage after immunization with the authorized vaccines, with two animals revealing unaffected, healthy lungs. No live virus was detectable in lung tissue in those vaccine groups, except for one animal with Vaxzevria. Our data reveal absence of induction of VAERD by the authorized vaccines in a susceptible hamster model, while the induced immune responses and observed degree of protection seem to match the clinical vaccine efficacy.