{ "abstract": "Phage therapy represents a promising strategy to tackle the growing threat of antimicrobial resistance. Increasing evidence has demonstrated that phage-specific antibodies may compromise the efficacy of phage therapy. Nevertheless, little is known about how phage protein specificity of antibodies modulates phage therapeutic outcomes. Herein, we utilized AbP20, a podovirus against Acinetobacter baumannii, to explore the effects of antibodies elicited by each structural protein on phage therapy efficacy in a mouse infection model. Intraperitoneal administration of AbP20 once a day for 7 consecutive days induced robust phage-specific antibody responses that impaired phage therapy. Genome-guided antigen screening identified that antibodies elicited by the nozzle and fiber proteins of AbP20, rather than those targeting the portal, capsid, or adaptor proteins, are the dominant drivers of phage therapy failure. Specifically, fiber-specific and nozzle-specific antibodies block bacterial adsorption and genomic injection of AbP20, respectively. Meanwhile, both antibody subsets efficiently induce large phage aggregates and potentiate macrophage phagocytosis via an Fc receptor-independent pathway. An evolved AbP20 variant with improved neutralization escape capacity exhibited comparable antibody-accelerated phagocytosis and host immune clearance, yet partially rescued therapeutic failure caused by neutralizing antibodies. Collectively, this study elucidates that nozzle- and fiber-elicited neutralizing antibodies impair phage therapy via dual synergistic mechanisms, which offers novel insights into the multifaceted modulation of phage-specific antibodies against phage therapeutic efficacy.\n\nPhage therapy can fail when the immune system makes antibodies against therapeutic viruses. This study shows that fiber- and nozzle-specific antibodies block phage infection and promote aggregation-driven, Fc receptor-independent phagocytosis.", "abstract_shown": true, "affiliations": [ "State Key Laboratory of Virology and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China", "University of Chinese Academy of Sciences, Beijing, China", "Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China", "Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland", "Faculty of Medicine, Wroclaw University of Science and Technology, Wrocław, Poland", "Hubei Jiangxia Laboratory, Wuhan, China" ], "article_type": "Research Article", "arxiv": null, "author_total": 10, "authors": [ { "affs": [ 0 ], "name": "Heng Xue" }, { "affs": [ 1 ], "name": "Xinfeng Li" }, { "affs": [ 2 ], "name": "Guibo Rao" }, { "affs": [ 3 ], "name": "Fen Hu" }, { "affs": [ 4 ], "name": "Mingyue Zhong" }, { "affs": [ 5 ], "name": "Paulina Miernikiewicz" }, { "name": "Rui Qiu" }, { "name": "Sheng Cao" }, { "name": "Krystyna Dąbrowska" }, { "name": "Hang Yang" } ], "bibtex": "https://research.draconitic.com/paper/7ytdt7tmrg6ja.bib", "cited_by": 0, "doi": "10.1371/journal.pbio.3004009", "fulltext_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004009", "id": "7ytdt7tmrg6ja", "issns": [ "1545-7885" ], "landing_url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004009", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2303|Bacteriophages and microbial interactions" ], [ "plos", "/Biology and life sciences/Anatomy/Body fluids/Blood/Blood serum/Immune serum" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Structural proteins" ], [ "plos", "/Biology and life sciences/Cell biology/Cell processes/Phagocytosis" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Immunology/Clinical immunology/Antibody therapy" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Biology and life sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Biology and life sciences/Organisms/Viruses/Bacteriophages" ], [ "plos", "/Biology and life sciences/Physiology/Body fluids/Blood/Blood serum/Immune serum" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Antibodies" ], [ "plos", "/Medicine and health sciences/Anatomy/Body fluids/Blood/Blood serum/Immune serum" ], [ "plos", "/Medicine and health sciences/Clinical medicine/Clinical immunology/Antibody therapy" ], [ "plos", "/Medicine and health sciences/Immunology/Clinical immunology/Antibody therapy" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Macrophages" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system proteins/Antibodies" ], [ "plos", "/Medicine and health sciences/Oncology/Cancer treatment/Antibody therapy" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Mouse models" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Mouse models" ], [ "plos", "/Research and analysis methods/Model organisms/Mouse models" ] ], "openalex": "W7214028788", "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3004009&type=printable", "pmcid": null, "pmid": null, "published": "2026-09-22", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/7ytdt7tmrg6ja.ris", "sources": [ { "first_seen": "2026-10-30T12:17:43Z", "native_id": "10.1371/journal.pbio.3004009", "source": "plos", "url": "https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3004009" } ], "subjects": [ { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "medicine", "origin": "plos:anatomy", "subfield": "physiology" } ], "title": "Antibodies targeting phage fiber and nozzle proteins impair Acinetobacter baumannii phage therapy by blocking infection and promoting immune clearance", "title_text": "Antibodies targeting phage fiber and nozzle proteins impair Acinetobacter baumannii phage therapy by blocking infection and promoting immune clearance", "type": "peer-reviewed", "updated_at": "2026-10-30T12:17:43Z", "url": "https://research.draconitic.com/paper/7ytdt7tmrg6ja", "venue": "PLOS Biology", "versions": [] }