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#mRNA-delivered neutralizing #antibodies confer protection against #SARS-CoV-2 in animal #models

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By G.M.

 


ABSTRACT

Monoclonal antibodies represent potent biological countermeasures against a wide range of human diseases; however, their clinical application and widespread use are limited by the high cost and complexity of antibody production and manufacturing. The mRNA-lipid nanoparticle (mRNA-LNP) platform offers a versatile strategy for vaccine development and protein-replacement therapies. Since the COVID-19 pandemic, a number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies have been identified, with several granted emergency use authorization for patients. Here, we report the design and generation of mRNA-LNPs encoding two SARS-CoV-2-neutralizing antibodies, 76E1 and LY1404, which, respectively, target the spike protein’s fusion peptide (FP) and receptor-binding domain (RBD). We demonstrated that a single intramuscular administration of these mRNA-LNPs in mice resulted in robust antibody production that sustained in circulation for 7–14 days. Furthermore, we evaluated protective effects of these mRNA-delivered antibodies in animal models and showed that a single IM dose of mRNA-LNPs encoding LY1404 or 76E1 conferred significant protection against multiple SARS-CoV-2 variants, including Omicron BQ.1 and Delta, in mice and hamsters. Collectively, these findings highlight the potential of mRNA-based antibody delivery for rapid prevention or treatment of pathogenic infections.

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Link: https://journals.asm.org/doi/full/10.1128/jvi.01897-25?af=R

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