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Front. Microbiol. | doi: 10.3389/fmicb.2018.03179

Lactic Acid Bacteria as a Live Delivery System for the In Situ Production of Nanobodies in the Human Gastrointestinal Tract

  • 1Spanish National Research Council (CSIC), Spain

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 - have 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.

Keywords: therapy, prophylaxis, Gastrointestinal Tract, in situ delivery, Lactic acid bacteria, nanobodies, VHH antibodies

Received: 26 Oct 2018; Accepted: 07 Dec 2018.

Edited by:

Paloma López, Centro de Investigaciones Biológicas (CIB), Spain

Reviewed by:

Daniela Fiocco, University of Foggia, Italy
Milan Kojic, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia  

Copyright: © 2018 del Rio, Redruello, Fernandez, Martin, Ladero and Alvarez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Beatriz del Rio, Spanish National Research Council (CSIC), Madrid, Spain, beadelrio@ipla.csic.es