De novo administration of antiviral monoclonal antibodies against SARS-CoV-2 or influenza using mRNA lipid nanoparticles

ABSTRACT Monoclonal antibodies (mAbs) are an emerging class of therapeutics for the prevention and treatment of viral infections. Recent advances in mRNA/lipid nanoparticle (LNP) technology provide a potential new modality for the expression of mAbs in vivo, potentially bypassing the need for recombinant manufacturing of mAb proteins. In this study, we compared traditional infusion of neutralising mAbs targeting SARS-CoV-2 or influenza to mRNA-based induction of de novo mAb expression in treated mice. High serum concentrations of mAbs were achieved upon delivery of a single mRNA encoding both heavy and light chains via intravenous or intramuscular routes using prototypic LNP formulations. However, pharmacokinetics were heavily influenced by the induction of anti-drug antibody responses directed against the encoded mAbs, driving reductions in in vivo half-life and compromising protective capacity against SARS-CoV-2 Omicron BA.1 infection. Overall, mRNA/LNP delivery comprises a feasible and attractive pathway to speed the development and deployment of antiviral antibodies, however optimisation of LNP formulation, dosing and administration routes is required to maximise protective potential.