An mRNA-based Expression of IgA Monoclonal Antibodies to Prevent Bacterial Infections

With the rapid advancement of mRNA delivery technology, the utilization of the mRNA platform for monoclonal antibody production has emerged as a cutting-edge approach to combating bacterial infections. In this strategy, the lipid nanoparticle (LNP)-mRNA platform can be employed to engineer the expression sequence of pathogen-specific immunoglobulin A (IgA) antibodies, which can be effectively administered into the human body to transform it into an IgA antibody factory that generates structurally and functionally intact human IgA molecules. These antibodies have demonstrated efficient delivery to mucosal secretions and successfully safeguard against Salmonella typhimurium and Pseudomonas aeruginosa 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 (rIgA) 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.

Fig.1 Delivery of nucleic acid antibodies is achieved through the injection of synthetic mRNA into cells.¹

The Future of mRNA-Encoded Antibodies in Disease Prevention and Treatment

An IgA monoclonal antibody recognizing the O-5 antigen of Salmonella typhimurium's lipopolysaccharide has been reported to effectively reduce the bacteria's intestinal invasion. An IgG1 binding to a component of the biofilm of Pseudomonas aeruginosa has also been reported, and its protective effects have been demonstrated in various animal models. The researchers encoded the heavy chain, light chain, and J chain of these antibodies into human IgA2 (IgA2 mRNA) or IgA1 (IgA1 mRNA), respectively. They then compared these with rIgA, both in vivo and in vitro, to evaluate the potential of mRNA platforms to produce potent and protective monoclonal antibodies in mucosal secretions. These studies revealed that, compared to rIgA, the mRNA-produced IgA showed a significantly prolonged serum half-life and a more natural glycosylation spectrum. Importantly, mRNA encoding IgA specific for Salmonella typhimurium significantly inhibits intestinal invasion by bacteria. Similarly, mRNA encoding IgA targeted for Pseudomonas aeruginosa provides successful protection against lung infections.

These findings imply that mRNA-encoded antibody technology could prove a powerful tool in intercepting bacterial pathogens on the mucosal surface, providing a new pathway for prevention and treatment interventions. These studies mark a significant step in the application of RNA technology and open up new horizons for further research and development in immunology and pathology.

At Creative Biolabs, we are not just a team, but a synergetic assembly of seasoned experts committed to offering a wide array of non-IgG antibody development services to our global clientele. Moreover, we don't just meet your unique needs, we decipher them by extending an extensive range of IgA antibodies stemming from diverse species such as humans, rats, mice, and bovine for sundry objectives. For any additional details aligned with your requirements, feel free to connect with us.

Reference

1. Patel, Ami, Mamadou A. Bah, and David B. Weiner. "In vivo delivery of nucleic acid-encoded monoclonal antibodies." BioDrugs 34.3 (2020): 273-293. Distributed under Open Access license CC BY 4.0, without modification.

---

• Non-IgG Therapeutic Antibodies Engineering
• Non-IgG Therapeutic Antibodies Discovery
• Production and Purification
• Non-IgG Therapeutic Antibodies Characterization
• Non-IgG Therapeutic Antibodies PK/PD Evaluation
• Developability Improvement

• IgA
• IgE
• IgM
• Assay kits

• Disease Therapy
• Clinical Diagnosis
• Non-IgG Antibody Application for Vaccine Development

• Non-IgG Antibody Related Diseases
• IgE Related Diseases
• Non-IgG Antibody Research Progress
• Non-IgG Antibody Isotypes
• Non-IgG Receptors and Interactions