Harnessing mRNA-encoded PcrV-targeting monoclonal antibodies for combating antibiotic-resistant Pseudomonas aeruginosa infections.

Abstract

The rising prevalence of antibiotic resistance, particularly among Pseudomonas aeruginosa strains, has become a substantial threat to public health. There is an urgent need for new therapeutics to tackle this challenge. This study explores the potential of mRNA-encoded monoclonal antibodies (mAbs) targeting the type III secretion system protein V (PcrV) antigen as a strategy to combat P. aeruginosa infections. We derived anti-PcrV mAbs from the B cells of immunized mice and identified two potent monoclonal antibodies (mAbs), M2C10 and M4C12 with the strongest binding affinity to PcrV. These mAbs were expressed, purified to high homogeneity, and encoded into mRNA for in vitro and in vivo functional assays. The results indicated that both mAbs exhibit high antibacterial activity in vitro. For in vivo efficacy, specific pathogen-free male BALB/c mice were used in acute systemic and pneumonia models. Survival, tissue bacterial loads, and histopathology were assessed. M2C10-mRNA outperformed M4C12-mRNA in increasing the survival rate of challenged mice, reducing tissue bacterial loads, and protecting against tissue damage in a murine model of acute infection. Collectively, our findings indicate that mRNA-encoded mAbs, particularly M2C10, offer a promising therapeutic strategy against P. aeruginosa, potentially serving as an alternative to conventional antibiotics and warrant further exploration.