Mucosal delivery of Lactococcus lactis carrying an anti-TNF scFv expression vector ameliorates experimental colitis in mice

Autor: Isabel Garcia Sousa, Anamélia Lorenzetti Bocca, Andrea Queiroz Maranhão, Vanessa Bastos Pereira, Marcelo M. Brigido, Mariana Gabriela Dantas de Azevedo, Maria José Chiabai, Juliana Franco Almeida, Leonora Maciel de Souza Vianna, Suelen Soares Fernandes, Raffael Júnio Araújo de Castro, Márcio Sousa Jerônimo, Anderson Miyoshi
Rok vydání: 2019
Předmět:
Zdroj: BMC Biotechnology, Vol 19, Iss 1, Pp 1-12 (2019)
BMC Biotechnology
ISSN: 1472-6750
DOI: 10.1186/s12896-019-0518-6
Popis: Background Anti-Tumor Necrosis Factor-alpha therapy has become clinically important for treating inflammatory bowel disease. However, the use of conventional immunotherapy requires a systemic exposure of patients and collateral side effects. Lactic acid bacteria have been shown to be effective as mucosal delivering system for cytokine and single domain antibodies, and it is amenable to clinical purposes. Therefore, lactic acid bacteria may function as vehicles for delivery of therapeutic antibodies molecules to the gastrointestinal tract restricting the pharmacological effect towards the gut. Here, we use the mucosal delivery of Lactococcus lactis carrying an anti-TNFα scFv expression plasmid on a DSS-induced colitis model in mice. Results Experimental colitis was induced with DSS administered in drinking water. L. lactis carrying the scFv expression vector was introduced by gavage. After four days of treatment, animals showed a significant improvement in histological score and disease activity index compared to those of untreated animals. Moreover, treated mice display IL-6, IL17A, IL1β, IL10 and FOXP3 mRNA levels similar to health control mice. Therefore, morphological and molecular markers suggest amelioration of the experimentally induced colitis. Conclusion These results provide evidence for the use of this alternative system for delivering therapeutic biopharmaceuticals in loco for treating inflammatory bowel disease, paving the way for a novel low-cost and site-specific biotechnological route for the treatment of inflammatory disorders. Electronic supplementary material The online version of this article (10.1186/s12896-019-0518-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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