Abstract
ABSTRACTInfluenza virus has pandemic potential, seasonal epidemics burden the human population, and viral resistance has developed to all available treatment options. A universally effective, escape mutant resistant therapeutic agent is desperately needed. We previously described extensive analyses of seven Matrix Protein 2 ectodomain-specific monoclonal antibodies (M2e-mAbs) as the basis for an effective and universal treatment for influenza A virus (IAV) infection. On the strength of these findings, we developed an effective prophylactic cocktail agent using three M2e-mAbs distinct in their M2e epitopes. This cocktail protected mice challenged with laboratory and pandemic IAV strains at a low dose significantly better than single M2e-mAb treatments. Notably, no viral escape mutants developed in immunocompetent and immunodeficient mice after viral passaging in the presence of single, cocktail, or alternating M2e-mAb treatments. Our study reveals the superiority of M2e-mAb cocktails, their universal effectiveness, and resistance to viral escape. It will critically shape future influenza-therapeutic development.
Publisher
Cold Spring Harbor Laboratory