Oral Application of T4 Phage Induces Weak Antibody Production in the Gut and in the Blood

Viruses

Joanna Majewska²  Weronika Beta²  Dorota Lecion²  Katarzyna Hodyra-Stefaniak²  Anna Kłopot²  Zuzanna Kaźmierczak²  Paulina Miernikiewicz²  Agnieszka Piotrowicz²  Jarosᐪw Ciekot²  Barbara Owczarek²  Agnieszka Kopciuch²  Karolina Wojtyna²  Marek Harhala²  Mateusz Mąkosa²  Krystyna Dၛrowska¹  Abram Aertsen² 

[1] Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, ul. R. Weigla 12, 53-114 Wrocław, Poland;

关键词: T4 phage;    EBOV;    Ebola virus;    oral administration;    vaccine;    phage display;    capsid proteins;    antibodies;    phage resistance;   

DOI  :  10.3390/v7082845

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
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