Lactic acid bacteria—20 years exploring their potential as live vectors for mucosal vaccination

Abstract

Lactic acid bacteria (LAB) are a diverse group of Gram-positive, nonsporulating, low G + C content bacteria. Many of them have been given generally regarded as safe status. Over the past two decades, intensive genetic and molecular research carried out on LAB, mainly Lactococcus lactis and some species of the Lactobacillus genus, has revealed new, potential biomedical LAB applications, including the use of LAB as adjuvants, immunostimulators, or therapeutic drug delivery systems, or as factories to produce therapeutic molecules. LAB enable immunization via the mucosal route, which increases effectiveness against pathogens that use the mucosa as the major route of entry into the human body. In this review, we concentrate on the encouraging application of Lactococcus and Lactobacillus genera for the development of live mucosal vaccines. First, we present the progress that has recently been made in the field of developing tools for LAB genetic manipulations, which has resulted in the successful expression of many bacterial, parasitic, and viral antigens in LAB strains. Next, we discuss the factors influencing the efficacy of the constructed vaccine prototypes that have been tested in various animal models. Apart from the research focused on an application of live LABs as carriers of foreign antigens, a lot of work has been recently done on the potential usage of nonliving, nonrecombinant L. lactis designated as Gram-positive enhancer matrix (GEM), as a delivery system for mucosal vaccination. The advantages and disadvantages of both strategies are also presented.

Non-conventional expression systems for the production of vaccine proteins and immunotherapeutic molecules

“…59 Since the early 1980s, gram-positive bacteria from the Bacillus or Lactococcus genera have been viewed as potential alternatives to E. coli for the production of recombinant proteins, their theoretical advantage being their capacity of secretion and relative adaptation to genetic manipulation. While there is an extensive literature on their use as expression systems, 60 and as live delivery vehicles for mucosal immunization, 61 data supporting their utility remains limited. Further investigation in this field is required.…”

Applications of Genetically Modified Immunobiotics with High Immunoregulatory Capacity for Treatment of Inflammatory Bowel Diseases

“…Lc. lactis was the first LAB species to have its whole genome sequenced, and there exists a wealth of genetic data on this species (8, 41, 42). In addition, Lc.…”

“…Genetic modification technology has undergone considerable advances in recent years, and Lactococcus ( Lc .) lactis in particular has been established as an efficient expression system for recombinant proteins (RPs) (8) (Figure 1A). Thus, probiotics, which have excellent safety and health advantages, are likely to be very useful as producers of IBD therapeutic proteins and as agents for delivering such proteins to the GIT (Figure 1B).…”

Lactobacillus pentosus expressing porcine lactoferrin elevates antibacterial activity and improves the efficacy of vaccination against Aujeszky’s disease

“…Many studies have shown that the use of the probiotic Lactobacillus as a vector delivery system has unmatched superiority compared to other known eukaryotes and prokaryotes (Wyszynska et al, 2015). In this research, using lactating porcine mammary tissue RNA as a template to obtain the N terminus pLF gene, we successfully obtained recombinant lactic acid bacteria expressing the pLF gene.…”