DNA-Delivered Monoclonal Antibodies Fight off Antibiotic Resistant Bacteria

Broad spectrum antibiotics have been used for decades to prevent all kinds of bacterial infections. However, they have recently been identified as a significant cause of the development of antimicrobial resistance bacteria (AMR). These microbes require a much more tailored treatment regime, as common antibiotics only seem to kill the normal microbiome, leaving the AMR’s to ravage the body at will. A new approach to AMR treatment is the development of microbiome friendly therapeutic monoclonal antibodies which initiate an immune response against foreign invaders without destroying the bodies natural flora. Therapeutic mAb’s have become a common approach to treat numerous kinds of infections, however, they come with their own set of difficulties. There are numerous limitations to IgG administration, dosage, production, and cost, leading researchers to turn to novel approaches of mAb administration.

One of these novel approaches is DNA-delivered mAb’s or DMAb’s. DMAb’s are DNA vectors which encode for a fully functional mAb. The vector is injected directly into the skeletal muscle via electroporation, where it can become transiently expressed, transcribed, translated, and secreted into the circulatory system. The mAb then acts identically as any other IgG molecule would, when injected into the blood of an infected individual. In order to use this system to treat patients infected with AMR’s, researchers at the Wistar Institute injected 2 different DMAb’s into mice infected with the AMR P. aeruginosa. The DMAb’s encoded 2 different mAb’s which were previously proven to be effective in treating P. aeruginosa, one targeting Psl (a protein important for immune evasion) and the other targeting both Psl and PcrV (important for host cell infection). Both DMAb’s showed similar potency to the control IgG injection as well as similar reductions in bacterial colonization, inflammation, pulmonary edema, bacterial quantity, and adjunctive activity when combined with antibiotics. The results of this study prove that DMAb’s are an optimal choice for AMR treatment as well as being considerably more cost effective while also minimizing the amount of mAb administrations.

Reference

• Patel, Ami, et al. "An engineered bispecific DNA-encoded IgG antibody protects against Pseudomonas aeruginosa in a pneumonia challenge model."  Nature Communications 8 (2017).