PT  - JOURNAL ARTICLE
AU  - Uri Elia
AU  - Shahar Rotem
AU  - Erez Bar-Haim
AU  - Srinivas Ramishetti
AU  - Gonna Somu Naidu
AU  - David Gur
AU  - Moshe Aftalion
AU  - Ma’ayan Israeli
AU  - Adi Bercovich-Kinori
AU  - Ron Alcalay
AU  - Efi Makdasi
AU  - Theodor Chitlaru
AU  - Ronit Rosenfeld
AU  - Tomer Israely
AU  - Sharon Melamed
AU  - Inbal Abutbul Ionita
AU  - Dganit Danino
AU  - Dan Peer
AU  - Ofer Cohen
TI  - A lipid nanoparticle RBD-hFc mRNA vaccine protects hACE2 transgenic mice against lethal SARS-CoV-2 infection
AID  - 10.1101/2021.03.29.436639
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.29.436639
4099  - http://biorxiv.org/content/early/2021/03/29/2021.03.29.436639.short
4100  - http://biorxiv.org/content/early/2021/03/29/2021.03.29.436639.full
AB  - The current global COVID-19 pandemic led to an unprecedented effort to develop effective vaccines against SARS-CoV-2. mRNA vaccines were developed very rapidly during the last year, and became the leading immunization platform against the virus, with highly promising phase-3 results and remarkable efficacy data. Since most animal models are not susceptible to SARS CoV-2 infection, pre-clinical studies are often limited to infection-prone animals such as hamsters and non-human primates. In these animal models, SARS-CoV-2 infection results in viral replication and a mild disease disease. Therefore, the protective efficacy of the vaccine in these animals is commonly evaluated by its ability to elicit immunologic responses, diminish viral replication and prevent weight loss. Our lab recently reported the design of a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs). These experiments demonstrated the development of a robust and specific immunologic response in RBD-hFc mRNA-vaccinated BALB/c mice. In the current study, we evaluated the protective effect of this RBD-hFc mRNA vaccine by employing the K18-hACE2 mouse model. We report that administration of RBD-hFc mRNA vaccine to K18-hACE2 mice led to a robust humoral response comprised of both binding and neutralizing antibodies. In accordance with the recorded immunologic immune response, 70% of vaccinated mice were protected against a lethal dose (3000 plaque forming units) of SARS-CoV-2, while all control animals succumbed to infection. To the best of our knowledge, this is the first non-replicating mRNA vaccine study reporting protection of K18-hACE2 against a lethal SARS-CoV-2 infection.Competing Interest StatementThe authors declare the following competing financial interest(s): D.P. receives licensing fees (to patents on which he was an inventor) from, invested in, consults (or on scientific advisory boards or boards of directors) for, lectured (and received a fee) or conducts sponsored research at TAU for the following entities: Alnylam Pharmaceuticals Inc., Arix Biosciences Inc., ART Biosciences, BioNtech RNA Pharmaceuticals, Centricus, Diagnostear Ltd., EPM Inc., Earli Inc., lmpetis Biosciences, Kernal Biologics, GPCR Inc., Medison Pharma Ltd., Newphase Ltd., NLC Pharma Ltd., Nanocell Therapeutics, NanoGhosts Ltd., Precision Nanosystems Inc., Paul Hastings Inc., Regulon, Roche, SciCann, Shire Inc., SirTLabs Corporation, VLX Ventures, TATA Cooperation, Teva Pharmaceuticals Inc., and Wize Pharma Ltd. All other authors declare no competing financial interests.