A pioneering study recently published in the Cell Reports Medicine, has demonstrated a groundbreaking approach to fighting bacterial infections. The research, titled "An mRNA-based platform for the delivery of pathogen-specific IgA into mucosal secretions," exploited a Lipid Nanoparticle (LNP) - mRNA platform to design pathogen-specific Immunoglobulin A (IgA) monoclonal antibodies. These antibodies were effectively delivered to mucosal secretions, yielding structurally and functionally intact human IgA, which successfully defends against Salmonella Typhimurium (STm) and Pseudomonas aeruginosa (PA) infections.
The Hurdles in Developing IgA and the Clinical Implementations of mRNA
The concept of passive immunization by using IgA is not a novelty; however, developing recombinant IgA (IgAR) and providing a sufficient quantity for consistent functioning pose significant challenges. Further complexities arise from the high glycosylation of human IgA proteins, which affects their conformation, thermal stability, folding efficiency, solubility, and susceptibility to proteolysis, making the production process difficult. The use of IgAR for most clinical applications is also problematic due to a shorter serum half-life compared to IgG, causing it to be removed from circulation more swiftly than endogenous human IgA. Therefore, the focus of numerous researchers has been to create an IgG/IgA chimera with desired Fc receptor interactions, extended serum half-life, and mucus delivery. Nevertheless, this has yet to reach the clinical stage. In contrast, the novel research introduced a new method that employs synthetic mRNA to produce structurally complete, functional human IgA in the body.
Learn more: An mRNA-based Expression of IgA Monoclonal Antibodies to Prevent Bacterial Infections
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