title: Oral Application of T4 Phage Induces Weak Antibody Production in the Gut and in the Blood.
abstract: A specific humoral response to bacteriophages may follow phage application for medical purposes, and it may further determine the success or failure of the approach itself. We present a long-term study of antibody induction in mice by T4 phage applied per os: 100 days of phage treatment followed by 112 days without the phage, and subsequent second application of phage up to day 240. Serum and gut antibodies (IgM, IgG, secretory IgA) were analyzed in relation to microbiological status of the animals. T4 phage applied orally induced anti-phage antibodies when the exposure was long enough (IgG day 36, IgA day 79); the effect was related to high dosage. Termination of phage treatment resulted in a decrease of IgA again to insignificant levels. Second administration of phage induces secretory IgA sooner than that induced by the first administrations. Increased IgA level antagonized gut transit of active phage. Phage resistant E. coli dominated gut flora very late, on day 92. Thus, the immunological response emerges as a major factor determining phage survival in the gut. Phage proteins Hoc and gp12 were identified as highly immunogenic. A low response to exemplary foreign antigens (from Ebola virus) presented on Hoc was observed, which suggests that phage platforms can be used in oral vaccine design.
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. joanna.majewska@iitd.pan.wroc.pl.
authors: Joanna
authors: J
authors: Majewska
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. weronika.beta@iitd.pan.wroc.pl.
authors: Weronika
authors: W
authors: Beta
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. lecion@iitd.pan.wroc.pl.
authors: Dorota
authors: D
authors: Lecion
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. katarzyna.hodyra@iitd.pan.wroc.pl.
authors: Katarzyna
authors: K
authors: Hodyra-Stefaniak
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. anna.klopot@iitd.pan.wroc.pl.
authors: Anna
authors: A
authors: Kłopot
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. zuzanna.kazmierczak@iitd.pan.wroc.pl.
authors: Zuzanna
authors: Z
authors: Kaźmierczak
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. pola@iitd.pan.wroc.pl.
authors: Paulina
authors: P
authors: Miernikiewicz
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. agnieszka.piotrowicz@gmail.com.
authors: Agnieszka
authors: A
authors: Piotrowicz
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. jaroslaw.ciekot@iitd.pan.wroc.pl.
authors: Jarosław
authors: J
authors: Ciekot
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. owczarek@iitd.pan.wroc.pl.
authors: Barbara
authors: B
authors: Owczarek
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. anna.klopot@iitd.pan.wroc.pl.
authors: Agnieszka
authors: A
authors: Kopciuch
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. karolina.wojtyna@gmail.com.
authors: Karolina
authors: K
authors: Wojtyna
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. marek.harhala@gmail.com.
authors: Marek
authors: M
authors: Harhala
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. mateusz.makosa@iitd.pan.wroc.pl.
authors: Mateusz
authors: M
authors: Mąkosa
authors: Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland. dabrok@iitd.pan.wroc.pl.
authors: Krystyna
authors: K
authors: Dąbrowska
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D017122:Bacteriophage T4 / Q000276:immunology*; D001769:Blood / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology; D029043:Ebolavirus / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000302:isolation & purification / Q000821:virology; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000821:virology*; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008137:Longitudinal Studies; D008297:Male; D008810:Mice, Inbred C57BL; D015678:Viral Structural Proteins / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; C108525:HOC protein, T4 phage; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015678:Viral Structural Proteins; C080832:gp12 protein, Enterobacteria phage T4
keywords: EBOV; Ebola virus; T4 phage; antibodies; capsid proteins; oral administration; phage display; phage resistance; vaccine