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

Deal, C. E.; Richards, A. F.; Yeung, T.; Maron, M. J.; Wang, Z.; Lai, Y.-T.; Fritz, B. R.; Himansu, S.; Narayanan, E.; Liu, D.; Koleva, R.; Licht, S.; Hsiao, C. J.; Rajlic, I. L.; Koch, H.; Kleyman, M.; Pulse, M. E.; Weiss, W. J.; Doering, J. E.; Lindberg, S. K.; Mantis, N. J.; Carfi, A.; Plante, O. J.

doi:10.1101/2023.01.03.521487

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bioRxiv · 10.1101/2023.01.03.521487

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

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Abstract

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

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Deal, C. E., Richards, A. F., Yeung, T., Maron, M. J., Wang, Z., Lai, Y.-T., Fritz, B. R., Himansu, S., Narayanan, E., Liu, D., Koleva, R., Licht, S., Hsiao, C. J., Rajlic, I. L., Koch, H., Kleyman, M., Pulse, M. E., Weiss, W. J., Doering, J. E., Lindberg, S. K., Mantis, N. J., Carfi, A., Plante, O. J.. 2023-01-03. mRNA delivery of dimeric human IgA protects mucosal tissues from bacterial infection. https://doi.org/10.1101/2023.01.03.521487

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