mRNA delivery of dimeric human IgA protects mucosal tissues from bacterial infection

Monoclonal antibody (mAb) therapy is a promising infectious disease intervention strategy but is limited to IgG1 isotypes that have restricted access to mucosal sites. IgA is well-established as the predominant antibody isotype in mucosal secretions but is clinically underutilized. To enable development of IgA-based mAbs, we exploited mRNA platform technology and demonstrated expression of functional, antigen-specific IgA (IgAmRNA) that can limit bacterial invasion in the intestine and prevent colonization in the lung. Moreover, in vivo IgAmRNA had enhanced serum half-life and a greater degree of sialylation than a recombinantly produced IgA. The results underscore the potential of mRNA-based platforms to deliver protective human mAbs to mucosal surfaces and open new avenues to combat infectious diseases in the face of pervasive antibiotic resistance. One Sentence SummarymRNA-encoded human monoclonal IgA traffics to mucosal tissues and provides protection against bacterial challenge