Antibody-Secreting Mesenchymal Stem Cells as a Next-Generation Immunotherapy for Influenza A

Influenza A (H1N1) remains a major global health concern, causing current outbreaks and seasonal epidemics. Despite widespread vaccination programs, the virus's high mutation rate results in frequent antigenic drift, limiting the durability of vaccines and antivirals. For instance, the 2024-2025 Canadian influenza vaccine demonstrated only 53% efficacy, underscoring the need for innovative, broad-spectrum therapies. This project aims to engineer mesenchymal stem cells (MSCs) to secrete neutralizing antibodies against H1N1. MSCs are an ideal therapeutic vehicle because they are easily sourced, immune-evasive, and possess intrinsic anti-inflammatory and regenerative properties. Their ability to home to injured lung tissue provides a means for localized and sustained delivery of therapeutic antibodies. By coupling antibody secretion with MSCs' immunomodulatory capacity, this approach could simultaneously neutralize viral particles and mitigate virus-induced inflammation. This study will employ the mouse-adapted PR8-H1N1 strain as a preclinical model. MSCs will be transduced with a plasmid encoding a broadly neutralizing antibody, enabling continuous antibody secretion. Following in-vitro validation of antibody production and viral neutralization, engineered MSCs will be administered to PR8-infected mice to assess antiviral efficacy, reduction of inflammation, and lung protection. This research will establish a proof-of-concept for antibody-secreting MSCs as a next generation immunotherapy, potentially replacing strain-specific vaccination with a versatile, cell-based platform that provides durable, broad-spectrum protection against diverse influenza A strains.