tetano
Editor, Senior Moderator
Mol Ther Nucleic Acids
. 2026 Feb 26;37(2):102873.
doi: 10.1016/j.omtn.2026.102873. eCollection 2026 Jun 16.
Delivery of monoclonal antibodies using mRNA lipid nanoparticles confers protection against SARS-CoV-2 and influenza
Mai N Vu[SUP] 1 [/SUP], Jessica A Neil[SUP] 1 [/SUP], Charley Mackenzie-Kludas[SUP] 1 [/SUP], Andrew Kelly[SUP] 1 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Kanta Subbarao[SUP] 1 [/SUP], Wen Shi Lee[SUP] 1 [/SUP], Adam K Wheatley[SUP] 1 [/SUP]
Affiliations
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.
. 2026 Feb 26;37(2):102873.
doi: 10.1016/j.omtn.2026.102873. eCollection 2026 Jun 16.
Delivery of monoclonal antibodies using mRNA lipid nanoparticles confers protection against SARS-CoV-2 and influenza
Mai N Vu[SUP] 1 [/SUP], Jessica A Neil[SUP] 1 [/SUP], Charley Mackenzie-Kludas[SUP] 1 [/SUP], Andrew Kelly[SUP] 1 [/SUP], Hyon-Xhi Tan[SUP] 1 [/SUP], Kanta Subbarao[SUP] 1 [/SUP], Wen Shi Lee[SUP] 1 [/SUP], Adam K Wheatley[SUP] 1 [/SUP]
Affiliations
- PMID: 41858837
- PMCID: PMC12996773
- DOI: 10.1016/j.omtn.2026.102873
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.