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 Summary mRNA-encoded human monoclonal IgA traffics to mucosal tissues and provides protection against bacterial challenge ### Competing Interest Statement CED, AFR, FR, TY, MJM, ZW, YL, BRF, SH, DL, RK, SL, CJH, ILR, HK, MK, AC, and OJP are employees of and shareholders in Moderna Inc. CED and OJP are co-inventors on international patent WO 2022/212191 A1. EN was an employee of and shareholder in Moderna Inc. at the time of the study. SKL, JED and NJM have no competing interests. MEP and WJW have no competing interests to report.