PEGylated human catalase elicits potent therapeutic effects on H1N1 influenza-induced pneumonia in mice

• Published in: Applied microbiology and biotechnology Vol. 97; no. 23; pp. 10025 - 10033
• Main Authors: Shi, Xunlong, Shi, Zhihui, Huang, Hai, Zhu, Hongguang, Zhu, Haiyan, Ju, Dianwen, Zhou, Pei
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.12.2013; Springer Berlin Heidelberg; Springer; Springer Nature B.V
• Subjects: Alzheimer's disease; Analysis; animal models; Animals; Atherosclerosis; Bacterial pneumonia; Biomedical and Life Sciences; Biotechnologically Relevant Enzymes and Proteins; Biotechnology; catalase; Catalase - administration & dosage; Catalase - chemistry; Catalysis; Disease Models, Animal; Enzymes; Ethylenediaminetetraacetic acid; Female; Genetic recombination; Humans; Infection; Infections; Influenza; Influenza A virus; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H1N1 Subtype - physiology; Influenza viruses; Influenza, Human - complications; Influenza, Human - virology; Injuries; Laboratory animals; Life Sciences; Male; Mice; Mice, Inbred ICR; Microbial Genetics and Genomics; Microbiology; Oxidative stress; Pandemics; Pharmaceuticals; Pharmacokinetics; Physiological aspects; Pneumonia; Pneumonia - drug therapy; Pneumonia - etiology; Pneumonia - metabolism; Polyethylene glycol; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; Polymers; Polyols; Proteins; reactive oxygen species; Reactive Oxygen Species - metabolism; Studies; Survival analysis; Swine flu; Swine influenza; therapeutics; virus replication; Viruses; China; Oxidative stress; Pneumonia; PEGylation; Catalase; Influenza
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-013-4775-3

Therapeutic recombinant human catalase (rhCAT) can quench infection-induced reactive oxygen species (ROS), thereby alleviating the associated tissue damage. Although the intranasal route is efficient to deliver native rhCAT to the lung, the therapeutic effect is limited by rapid elimination from the blood. In this study, we modified rhCAT with the active polymer, polyethylene glycol monomethyl ether (PEG)-5000, and analyzed the pharmacokinetics of PEGylated rhCAT in mice. The high tetra-PEGylation ratio was about 60 %, and PEGylation prolonged the half-life of rhCAT in serum (75 vs. 13.5 min for native rhCAT). The protective effects of PEG-rhCAT were investigated in a mouse model of influenza virus A (H1N1)-associated pneumonia. PEG-rhCAT was more effectively delivered than native rhCAT and was associated with higher survival ratio, less extensive lung injuries, reduced ROS levels, and lower viral replication. Collectively, these findings indicate that PEGylation can enhance the therapeutic efficacy of native rhCAT and suggest that PEGylated rhCAT may represent a novel complement therapy for H1N1 influenza-induced pneumonia.