Intranasal phage therapy overcomes antibody neutralization challenges in pulmonary Pseudomonas aeruginosa infections
1
Issued Date
2025-12-01
Resource Type
ISSN
03028933
eISSN
1432072X
Scopus ID
2-s2.0-105019114540
Pubmed ID
41108387
Journal Title
Archives of Microbiology
Volume
207
Issue
12
Rights Holder(s)
SCOPUS
Bibliographic Citation
Archives of Microbiology Vol.207 No.12 (2025)
Suggested Citation
Wannigama D.L., Shao J., Sun H., Wang Y., Hurst C., Monk P.N., Amarasiri M., Phattharapornjaroen P., Ditcham W.G.F., Htun T.S., Luk-in S., Shimotai Y., Ngamwongsatit N., Ishikawa H., Ragupathi N.K.D., Pletzer D., Kanjanabuch T., Khatib A., Miyanaga K., Cui L., Shibuya K., Higgins P.G., Kicic A., Hongsing P., Zhao J., Abe S., Hamamoto H. Intranasal phage therapy overcomes antibody neutralization challenges in pulmonary Pseudomonas aeruginosa infections. Archives of Microbiology Vol.207 No.12 (2025). doi:10.1007/s00203-025-04526-6 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/112763
Title
Intranasal phage therapy overcomes antibody neutralization challenges in pulmonary Pseudomonas aeruginosa infections
Author(s)
Wannigama D.L.
Shao J.
Sun H.
Wang Y.
Hurst C.
Monk P.N.
Amarasiri M.
Phattharapornjaroen P.
Ditcham W.G.F.
Htun T.S.
Luk-in S.
Shimotai Y.
Ngamwongsatit N.
Ishikawa H.
Ragupathi N.K.D.
Pletzer D.
Kanjanabuch T.
Khatib A.
Miyanaga K.
Cui L.
Shibuya K.
Higgins P.G.
Kicic A.
Hongsing P.
Zhao J.
Abe S.
Hamamoto H.
Shao J.
Sun H.
Wang Y.
Hurst C.
Monk P.N.
Amarasiri M.
Phattharapornjaroen P.
Ditcham W.G.F.
Htun T.S.
Luk-in S.
Shimotai Y.
Ngamwongsatit N.
Ishikawa H.
Ragupathi N.K.D.
Pletzer D.
Kanjanabuch T.
Khatib A.
Miyanaga K.
Cui L.
Shibuya K.
Higgins P.G.
Kicic A.
Hongsing P.
Zhao J.
Abe S.
Hamamoto H.
Author's Affiliation
The University of Queensland
Monash University
Tohoku University
The University of Sheffield
University of Toronto Faculty of Medicine
University of Otago
Mahidol University
Ningbo University
Jichi Medical University
Thammasat University
The Faculty of Health Sciences
Yamagata University Faculty of Medicine
The Kids Research Institute Australia
The Sheffield Medical School
Medizinische Fakultät
King Chulalongkorn Memorial Hospital
UWA Medical School
Faculty of Medicine, Chulalongkorn University
WPI Immunology Frontier Research Center, The University of Osaka
Faculty of Medicine, Thammasat University
Perth Children's Hospital
Chulabhorn Royal Academy
Yamagata Prefectural Central Hospital
The Tokyo Foundation for Policy Research
Yamagata Prefectural University of Health Sciences
Hospital of Chongqing University
Partner Site Bonn-Cologne
Zhejiang University
Bioberrys Healthcare and Research Centre
Monash University
Tohoku University
The University of Sheffield
University of Toronto Faculty of Medicine
University of Otago
Mahidol University
Ningbo University
Jichi Medical University
Thammasat University
The Faculty of Health Sciences
Yamagata University Faculty of Medicine
The Kids Research Institute Australia
The Sheffield Medical School
Medizinische Fakultät
King Chulalongkorn Memorial Hospital
UWA Medical School
Faculty of Medicine, Chulalongkorn University
WPI Immunology Frontier Research Center, The University of Osaka
Faculty of Medicine, Thammasat University
Perth Children's Hospital
Chulabhorn Royal Academy
Yamagata Prefectural Central Hospital
The Tokyo Foundation for Policy Research
Yamagata Prefectural University of Health Sciences
Hospital of Chongqing University
Partner Site Bonn-Cologne
Zhejiang University
Bioberrys Healthcare and Research Centre
Corresponding Author(s)
Other Contributor(s)
Abstract
Phage therapy is a promising approach against multidrug-resistant infections, yet systemic administration can lead to incomplete cures. We investigated the distribution, immune responses, and efficacy of the therapeutic phage KPP10 delivered via intranasal or intraperitoneal (IP) routes in murine Pseudomonas aeruginosa lung infection models. Intranasal pre-treatment achieved markedly higher localization of KPP10 in the lungs and bronchoalveolar compartment compared to IP delivery. Intranasal administration elicited minimal systemic antibody responses, whereas IP injection triggered significant IgG, IgM, and IgA production. Antibody responses did not differ significantly between doses. In acute and chronic infection models, intranasal KPP10 significantly improved survival (p < 0.01) and reduced lung bacterial loads relative to IP injection. Importantly, IP treatment was associated with bacterial rebound after day 14 in chronic infection, whereas intranasal dosing sustained bacterial clearance. These findings demonstrate that intranasal delivery enhances pulmonary localization, minimizes antibody-mediated neutralization, and provides superior therapeutic efficacy, highlighting its potential as a more effective route for phage therapy against P. aeruginosa lung infections.