Delivery of monoclonal antibodies using mRNA lipid nanoparticles confers protection against SARS-CoV-2 and influenza

Mai N Vu; Jessica A Neil; Charley Mackenzie-Kludas; Andrew Kelly; Hyon-Xhi Tan; Kanta Subbarao; Wen Shi Lee; Adam K Wheatley

doi:10.1016/j.omtn.2026.102873

Delivery of monoclonal antibodies using mRNA lipid nanoparticles confers protection against SARS-CoV-2 and influenza

Mol Ther Nucleic Acids. 2026 Feb 26;37(2):102873. doi: 10.1016/j.omtn.2026.102873. eCollection 2026 Jun 16.

Authors

Mai N Vu¹, Jessica A Neil¹, Charley Mackenzie-Kludas¹, Andrew Kelly¹, Hyon-Xhi Tan¹, Kanta Subbarao¹, Wen Shi Lee¹, Adam K Wheatley¹

Affiliation

¹ Department of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.

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 promising new modality for the production of mAbs in vivo, potentially bypassing the need for recombinant manufacturing of mAb proteins. In this study, we compared traditional infusion of protein-based neutralizing mAbs targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or influenza viruses to mRNA/LNP-based production of mAbs 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, the pharmacokinetics of mRNA-delivered mAbs were heavily influenced by the induction of anti-drug antibody responses directed against the encoded mAbs, resulting in reduced half-life in vivo and compromised protective capacity against SARS-CoV-2 Omicron BA.1 infection. In contrast, mRNA/LNP delivery of a neutralizing mAb conferred superior protection against lethal influenza challenge compared to equivalent recombinant protein doses. Overall, mRNA/LNP delivery comprises a feasible and attractive pathway to speed the development and deployment of antiviral antibodies. However, optimization of LNP formulation, dosing, and administration routes is required to maximize protective potential.

Keywords: MT: Delivery Strategies; SARS-CoV-2; administration routes; anti-drug antibody; influenza; mRNA design; mRNA lipid nanoparticle; monoclonal antibody.