Evaluating the Efficacy of mRNA Vaccine Platforms Against Rapidly Mutating Equine Influenza Virus Strains: A Controlled Comparative Immunogenicity Study

Abstract

The increasing genetic variability of equine influenza virus (EIV) presents a persistent challenge to effective disease control through traditional vaccine platforms. This study evaluated the immunogenicity, safety, and adaptability of a lipid nanoparticle-encapsulated mRNA vaccine targeting the H3N8 subtype of EIV in a controlled experimental trial involving 30 horses. Subjects were divided into three cohorts (mRNA vaccine, inactivated vaccine, and placebo), and immunological responses were assessed over a 60-day period through ELISA, virus-neutralization assays, flow cytometry, ELISpot, and RT-PCR. Results demonstrated that the mRNA vaccine group elicited significantly higher IgG titers, superior virus-neutralizing activity, and enhanced CD4⁺/CD8⁺ T cell activation compared to controls. Cytokine expression (IFN-γ, IL-4, TNF-α) was significantly elevated, and antibody decay analysis revealed prolonged immune durability. Importantly, the mRNA vaccine also induced robust cross-neutralization against heterologous EIV strains, suggesting broader protective efficacy. Adverse effects were minimal and limited to transient local reactions. Collectively, the findings highlight the potential of mRNA vaccine platforms to address the limitations of traditional immunization strategies by offering rapid adaptability, potent immunity, and a favorable safety profile. This positions mRNA vaccines as a promising next-generation approach for the control of evolving EIV outbreaks and potentially other equine viral threats.