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

## TL;DR

Scientists used mRNA lipid nanoparticles to produce antibodies in mice, offering protection against SARS-CoV-2 and influenza, but found that immune responses reduced their effectiveness.

## Contribution

This study demonstrates in vivo production of neutralizing monoclonal antibodies using mRNA/LNPs as an alternative to traditional protein manufacturing.

## Key findings

- mRNA/LNPs delivered high serum concentrations of monoclonal antibodies in mice.
- Anti-drug antibodies reduced the half-life and protective capacity of SARS-CoV-2 antibodies.
- mRNA/LNP-delivered antibodies provided better protection against influenza than recombinant proteins.

## 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.

mRNA lipid nanoparticle delivery enables in vivo production of neutralizing monoclonal antibodies against SARS-CoV-2 and influenza at serum levels comparable to recombinant proteins. However, anti-drug antibody responses limit their durability, highlighting the need to optimize lipid nanoparticle formulation and administration routes to maximize antibody accumulation, retention, and mucosal localization.