Use of genetically modified lactic acid bacteria and bifidobacteria as live delivery vectors for human and animal health

Abstract

There is now strong evidence to support the interest in using lactic acid bacteria (LAB)in particular, strains of lactococci and lactobacilli, as well as bifidobacteria, for the development of new live vectors for human and animal health purposes. LAB are Gram-positive bacteria that have been used for millennia in the production of fermented foods. In addition, numerous studies have shown that genetically modified LAB and bifodobacteria can induce a systemic and mucosal immune response against certain antigens when administered mucosally. They are therefore good candidates for the development of new mucosal delivery strategies and are attractive alternatives to vaccines based on attenuated pathogenic bacteria whose use presents health risks. This article reviews the most recent research and advances in the use of LAB and bifidobacteria as live delivery vectors for human and animal health.

Recent advances in genetic tools for engineering probiotic lactic acid bacteria

“…lactis NCDO2118 inducible xylose permease gene promoter (PxylT) [ 145 , 154 ]. The XIES can be activated or repressed by adding either xylose or glucose, respectively [ 155 ]. XIES has two versions: a cytoplasmic variant, for production of intracellular proteins, and a secreted variant, for secretion of proteins [ 156 ].…”

“…SICE is induced by harsh environmental conditions such as high salt concentration, ultraviolet (UV) irradiation, low pH, or heat shock, and is based on the Lc. lactis groESL heat shock protein promoter [ 155 ]⁠. Stresses that are encountered by engineered probiotics during GIT transit, such as acid stress, biliary stress, and heat stress, can induce expression in this system and allow the in situ production of the heterologous proteins of interest [ 155 ].…”

Recombinant Helicobacter pylori Vaccine Delivery Vehicle: A Promising Tool to Treat Infections and Combat Antimicrobial Resistance

“…Plasmid loss or instability in the bacterial vaccine carrier compromises the expression and delivery of antigens, and ultimately immune response. Furthermore, inducible expression systems have been incorporated in these vectors in order to provide a controlled expression of vaccine constructs and find an optimal balance between antigen production and bacterial fitness in host organs [ 62 , 63 , 64 ].…”

“…The antibiotic-free vectors have been widely in the two existing categories of bacterial vaccine delivery vehicles including attenuated pathogens and non-pathogenic/commensal bacteria, the most represented species of the two types being Salmonella [ 64 ] and Lactococcus lactis [ 63 ]. We describe below the balanced-lethal vector-host system developed in Salmonella , a vehicle of the same category as H. pylori , as an example of one of the most attracting systems that serve as both antibiotic-free and stabilization systems and additionally enable within-host inducible expression of vaccine construct.…”

“…Cytokines represent a third class of adjuvant that can be considered for the Hp vaccine carrier. Co-delivery of antigen with cytokines has been tested with other bacterial vaccine carriers including attenuated pathogens [ 106 ] and commensal bacteria [ 63 , 66 ] resulting in enhanced immune responses against the antigen. The interest in co-delivery of cytokine with antigen lies in that this class of adjuvant represents an efficient means of directing immune activation toward a desired type of response.…”