Development of an Antigen Delivery Platform Using Lactobacillus acidophilus Decorated With Heterologous Proteins: A Sheep in Wolf's Clothing Story.
| Autor: | Uriza PJ; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, IIB-UNSAM (IIBIO-CONICET), Buenos Aires, Argentina., Trautman C; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, IIB-UNSAM (IIBIO-CONICET), Buenos Aires, Argentina., Palomino MM; Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina.; CONICET - Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina., Fina Martin J; Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina.; CONICET - Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina., Ruzal SM; Facultad de Ciencias Exactas y Naturales, Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires, Argentina.; CONICET - Universidad de Buenos Aires, Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Buenos Aires, Argentina., Roset MS; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, IIB-UNSAM (IIBIO-CONICET), Buenos Aires, Argentina., Briones G; Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, IIB-UNSAM (IIBIO-CONICET), Buenos Aires, Argentina. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in microbiology [Front Microbiol] 2020 Oct 27; Vol. 11, pp. 509380. Date of Electronic Publication: 2020 Oct 27 (Print Publication: 2020). |
| DOI: | 10.3389/fmicb.2020.509380 |
| Abstrakt: | S-layers are bacterial structures present on the surface of several Gram-positive and Gram-negative bacteria that play a role in bacterial protection. In Lactobacillus acidophilus ( L. acidophilus ATCC 4356), the S-layer is mainly composed of the protein SlpA. A tandem of two copies of the protein domain SLP-A (pfam: 03217) was identified at the C-terminal of SlpA, being this double SLP-A protein domain (in short dSLP-A) necessary and sufficient for the association of the protein to the L. acidophilus cell wall. A variety of proteins fused to the dSLP-A domain were able to spontaneously associate with high affinity to the cell wall of L. acidophilus and Bacillus subtilis var. natto, in a process that we termed decoration. Binding of dSLP-A-containing-proteins to L. acidophilus was stable at conditions that mimic the gastrointestinal transit in terms of pH, proteases, and bile salts. To evaluate if protein decoration of L. acidophilus can be adapted to generate an oral vaccine platform, a chimeric antigen derived from the bacterial pathogen Shiga-toxin-producing Escherichia coli (STEC) was constructed by fusing the sequences encoding the polypeptides EspA 36-192 , Intimin 653-953 , Tir 240-378 , and H7 flagellin 352-374 (EITH7) to the dSLP-A domain (EITH7-dSLP-A). Recombinantly expressed EITH7-dSLP-A protein was affinity purified and combined with L. acidophilus cultures to allow the association of the chimeric antigen to the bacterial surface. EITH7-decorated L. acidophilus was orally administered to BALB/c mice and the induction of anti-EITH7 specific antibodies in sera and feces determined by ELISA. Mice presenting significantly higher anti-EITH7 antibodies titers were able to control more efficiently an experimental STEC infection than mice that received the non-decorated L. acidophilus carrier, indicating that antigen-decorated L. acidophilus can be adapted as a mucosal immunization delivery platform to elicit a protective immune response for vaccine purposes. (Copyright © 2020 Uriza, Trautman, Palomino, Fina Martin, Ruzal, Roset and Briones.) |
| Databáze: | MEDLINE |
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