Authors
Xin Xia, Juhao Yang, Deli Shang, Tingting Tang, Yaya Zhao, Hailin Wei, Fusong Wu, Kuan Tang, Xiaoping Bian, Feng Yang
Published in
Infection and drug resistance. Volume 19. Pages 630080. Epub Aug 23, 2026.
Abstract
Pseudomonas aeruginosa (P. aeruginosa) pose a global health threat, with carbapenem-resistant strains in particular posing a grave threat due to high mortality rates and limited treatment options for antibiotic-refractory infections. To address the inherent limitations of single-target therapies, this study developed a multi-target fully human monoclonal antibody (mAb) cocktail targeting three core virulence factors: a key component of the type III secretion system, exotoxin A, and an outer membrane protein. Using a fully human transgenic mouse platform, we generated and characterized three high-affinity mAbs targeting PcrV (U0151, Kd = 2.69 nM), ETA (U0462, Kd = 1.75 nM), and PA0833 (U0057, Kd = 0.34 nM). Functional assays confirmed robust target-specific activities, including neutralization of PcrV-mediated hemolysis, inhibition of ETA-induced cytotoxicity, and enhancement of cell-mediated bacterial clearance. In mouse models of systemic infection and acute pneumonia caused by PAO1, a significant enhancement in efficacy was observed when three types of antibodies were used in combination, increasing protective rates to 78% and 88%, respectively, whereas monotherapies achieved protective rates of no more than 38%. Combined treatment also reduced bacterial burden, alleviated tissue damage, and suppressed excessive neutrophil infiltration. Furthermore, it showed immune protection against several clinical isolates of P. aeruginosa, including carbapenem-resistant strains, within these limits, the data support the three-antibody combination as a candidate adjunctive immunotherapy for multidrug-resistant P. aeruginosa infection.
PMID:
42662857
Bibliographic data and abstract were imported from PubMed on 28 Aug 2026.
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