Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection.
Uri EliaShahar RotemErez Bar-HaimSrinivas RamishettiGonna Somu NaiduDavid GurMoshe AftalionMa'ayan IsraeliAdi Bercovich-KinoriRon AlcalayEfi MakdasiTheodor ChitlaruRonit RosenfeldTomer IsraelySharon MelamedInbal Abutbul IonitaDganit DaninoDan PeerOfer CohenPublished in: Nano letters (2021)
The COVID-19 pandemic led to development of mRNA vaccines, which became a leading anti-SARS-CoV-2 immunization platform. Preclinical studies are limited to infection-prone animals such as hamsters and monkeys in which protective efficacy of vaccines cannot be fully appreciated. We recently reported a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs). BALB/c mice demonstrated specific immunologic responses following RBD-hFc mRNA vaccination. Now, we evaluated the protective effect of this RBD-hFc mRNA vaccine by employing the K18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model. Administration of an RBD-hFc mRNA vaccine to K18-hACE2 mice resulted in robust humoral responses comprising binding and neutralizing antibodies. In correlation with this response, 70% of vaccinated mice withstood a lethal SARS-CoV-2 dose, while all control animals succumbed to infection. To the best of our knowledge, this is the first nonreplicating mRNA vaccine study reporting protection of K18-hACE2 against a lethal SARS-CoV-2 infection.
Keyphrases
- sars cov
- binding protein
- respiratory syndrome coronavirus
- endothelial cells
- mouse model
- angiotensin converting enzyme
- healthcare
- high fat diet induced
- immune response
- type diabetes
- emergency department
- stem cells
- high throughput
- fatty acid
- photodynamic therapy
- mesenchymal stem cells
- skeletal muscle
- metabolic syndrome
- bone marrow
- insulin resistance
- dna binding