Lactic acid bacteria as a live delivery system for the in situ production of nanobodies in the human gastrointestinal tract

Lactic acid bacteria (LAB) are among the most widely used microorganisms in food fermentation. However, some LAB species can also be used as live vehicles for the in situ delivery of therapeutic molecules to the mucosa of the human gastrointestinal tract (GIT). Many LAB species have ‘qualified presu...

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Detalhes bibliográficos
Autores: Río Lagar, Beatriz del, Redruello, Begoña, Fernández García, María, Martín, M. Cruz, Ladero Losada, Víctor Manuel, Álvarez González, Miguel Ángel
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2019
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/186178
Acesso em linha:http://hdl.handle.net/10261/186178
Access Level:Acceso aberto
Palavra-chave:VHH
Nanobodies
Lactic acid bacteria
In situ delivery
Gastrointestinal tract
Prophylaxis
Therapy
Descrição
Resumo:Lactic acid bacteria (LAB) are among the most widely used microorganisms in food fermentation. However, some LAB species can also be used as live vehicles for the in situ delivery of therapeutic molecules to the mucosa of the human gastrointestinal tract (GIT). Many LAB species have ‘qualified presumption of safety’ status and survive passage through the GIT. Indeed, some are part of the usual GIT microbiota. These are appropriate candidates for the in situ production of recombinant prophylactic and therapeutic proteins. Live recombinant LAB that produce microbial antigens have been shown to elicit an immune response that confers protection against the corresponding pathogens; these LAB could therefore be used as oral vaccines. In addition, some LAB have been genetically engineered to produce therapeutic, neutralizing antibodies. The variable domain of heavy-chain-only antibodies from camelids – known as VHH antibodies or nanobodies – has peculiar properties (nanoscale size, robust structure, acid resistance, high affinity and specificity, easily produced in bacteria, etc.) that make them ideal choices as LAB-produced immunotherapeutic agents. The present review examines the advantages offered by LAB for the in situ production of therapeutic proteins in the human GIT, discusses the use of in situ produced VHH antibody fragments, and assesses the usefulness of this strategy in the treatment of infectious and non-infectious gastrointestinal diseases.