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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Surface Display of an Anti-CD3 scFv by Saccharomyces boulardii and Its Effect on DSS-Induced Colitis in Mice

  • Sylvia Barbosa Pinhate1,2
  • Pietra Oliveira Guimarães1,3
  • Isabel Garcia Sousa1
  • Manuela Maragno do Almo1
  • Renato Rodrigues Oliveira1,2
  • Ana Luiza Tancredi de Matos1
  • Andréa Queiroz Maranhão1,4
  • Marcelo Macedo Brigido1,4
4 affiliations
  1. 1Molecular Immunology Group, Department of Cell Biology, University of Brasília, Brasília 70910-900, DF, Brazil
  2. 2Molecular Biology Graduate Program, Biology Institute, University of Brasília, Brasília 70910-900, DF, Brazil
  3. 3Molecular Pathology Graduate Program, Faculty of Medicine, University of Brasília, Brasília 70910-900, DF, Brazil
  4. 4National Institute of Science and Technology of Mucosa and Skin, Belo Horizonte 31270-901, MG, Brazil
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Abstract

Saccharomyces boulardii (Sb) is a probiotic yeast amenable to genetic manipulation, making it a promising platform for delivery of recombinant biotherapeutics to the intestinal lumen. In this study, we engineered a recombinant Sb strain to display an anti-CD3 single-chain variable fragment (scFv) on its surface and evaluated its potential as an oral antibody delivery system. To improve antibody accessibility, we tested different stalk lengths between the scFv and the SED1 anchoring domain. The strain with the longer stalk domain (Sb649) showed more stable surface display over time and was subsequently evaluated in a dextran sulfate sodium (DSS)-induced colitis model. Sb649-treated mice showed body weight values and disease activity profiles closer to those of healthy controls. Sb649 administration was also associated with transcriptional changes, including increased Foxp3 expression and no increase in Il6 in mesenteric lymph nodes, unlike DSS and DSS+SbWT-treated mice, along with increased Muc3 expression in the colon compared to DSS-treated mice. Together, these findings show that engineered Sb can stably display antibody fragments and support its potential as a platform for oral delivery of antibody-based immunotherapies to the gastrointestinal tract.

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Cite

BibTeXRIS
BibTeX
@article{pinhate2026surface,
  title = {{Surface Display of an Anti-CD3 scFv by Saccharomyces boulardii and Its Effect on DSS-Induced Colitis in Mice}},
  author = {Sylvia Barbosa Pinhate and Pietra Oliveira Guimarães and Isabel Garcia Sousa and Manuela Maragno do Almo and Renato Rodrigues Oliveira and Ana Luiza Tancredi de Matos and Andréa Queiroz Maranhão and Marcelo Macedo Brigido},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27208959},
  url = {https://www.mdpi.com/1422-0067/27/20/8959},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Surface Display of an Anti-CD3 scFv by Saccharomyces boulardii and Its Effect on DSS-Induced Colitis in Mice
AU  - Sylvia Barbosa Pinhate
AU  - Pietra Oliveira Guimarães
AU  - Isabel Garcia Sousa
AU  - Manuela Maragno do Almo
AU  - Renato Rodrigues Oliveira
AU  - Ana Luiza Tancredi de Matos
AU  - Andréa Queiroz Maranhão
AU  - Marcelo Macedo Brigido
PY  - 2026
DA  - 2026/10/09
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27208959
UR  - https://www.mdpi.com/1422-0067/27/20/8959
AB  - Saccharomyces boulardii (Sb) is a probiotic yeast amenable to genetic manipulation, making it a promising platform for delivery of recombinant biotherapeutics to the intestinal lumen. In this study, we engineered a recombinant Sb strain to display an anti-CD3 single-chain variable fragment (scFv) on its surface and evaluated its potential as an oral antibody delivery system. To improve antibody accessibility, we tested different stalk lengths between the scFv and the SED1 anchoring domain. The strain with the longer stalk domain (Sb649) showed more stable surface display over time and was subsequently evaluated in a dextran sulfate sodium (DSS)-induced colitis model. Sb649-treated mice showed body weight values and disease activity profiles closer to those of healthy controls. Sb649 administration was also associated with transcriptional changes, including increased Foxp3 expression and no increase in Il6 in mesenteric lymph nodes, unlike DSS and DSS+SbWT-treated mice, along with increased Muc3 expression in the colon compared to DSS-treated mice. Together, these findings show that engineered Sb can stably display antibody fragments and support its potential as a platform for oral delivery of antibody-based immunotherapies to the gastrointestinal tract.
SN  - 1422-0067
ER  -