040efc28-9efa-4f0f-bd9e-e69e3b3c0d31
Complete protection against both SARS-CoV-2 lineage B BavPat1 and novel B.1.351 by mRNA immunization in a transgenic mouse model
The SARS-CoV-2 pandemic r esulted in countless illnesses and millions of deaths and vaccines are the primary control option. However, recently virus mutants termed “variants of concern” (VOC) emerged with the potential to escape host immunity. VOC B.1.351 has been first discovered in South Africa in late 2020 and causes global concern due to poor neutralization and its propensity to cause reinfections. We tested in a K18-hACE2 transgenic mouse model the efficacy of a spike protein encoding mRNA vaccine (CVnCoV) in parallel against the ancestral strain BavPat1 and the novel VOC B.1.351. Naïive mice and mice receiving a formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA immunized mice developed elevated SARS-CoV-2 RBD-specific antibody titers but showed a significant reduction of neutralization titers when tested against VOC B.1.351. Interestingly, VOC B.1.351-infected control animals experienced a delayed course of disease, yet nearly all SARS-CoV-2 challenged naïve mice succumb with virus dissemination and high viral loads. CVnCoV vaccine completely protected the animals from clinical disease and mortality caused by either virus strain. Moreover, SARS-CoV-2 was not detected in oral swabs, lung and brain in these groups. Only partial protection was observed in mice receiving the formalin-inactivated virus preparation. Overall, our studies show complete clinical protection against novel VOC with immune-escape properties like B.1.351 although neutralizing antibody titers are lower than against the ancestral strain.
The SARS-CoV-2 pandemic r esulted in countless illnesses and millions of deaths and vaccines are the primary control option. However, recently virus mutants termed “variants of concern” (VOC) emerged with the potential to escape host immunity. VOC B.1.351 has been first discovered in South Africa in late 2020 and causes global concern due to poor neutralization and its propensity to cause reinfections. We tested in a K18-hACE2 transgenic mouse model the efficacy of a spike protein encoding mRNA vaccine (CVnCoV) in parallel against the ancestral strain BavPat1 and the novel VOC B.1.351. Naïive mice and mice receiving a formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA immunized mice developed elevated SARS-CoV-2 RBD-specific antibody titers but showed a significant reduction of neutralization titers when tested against VOC B.1.351. Interestingly, VOC B.1.351-infected control animals experienced a delayed course of disease, yet nearly all SARS-CoV-2 challenged naïve mice succumb with virus dissemination and high viral loads. CVnCoV vaccine completely protected the animals from clinical disease and mortality caused by either virus strain. Moreover, SARS-CoV-2 was not detected in oral swabs, lung and brain in these groups. Only partial protection was observed in mice receiving the formalin-inactivated virus preparation. Overall, our studies show complete clinical protection against novel VOC with immune-escape properties like B.1.351 although neutralizing antibody titers are lower than against the ancestral strain.