Adjuvant Strategies for Lactic Acid Bacterial Mucosal Vaccines

Abstract

Lactic acid bacteria (LAB) are Gram-positive, acid-tolerant bacteria that have long been used in food fermentation and are generally recognized as safe (GRAS). LAB are a part of a normal microbiome and act as probiotics, improving the gastrointestinal microbiome and health when consumed. An increasing body of research has shown the importance of the microbiome on both mucosal immune heath and immune response to pathogens and oral vaccines. Currently, there are few approved mucosal vaccines, and most are attenuated viruses or bacteria, which necessitates cold chain, carries the risk of reversion to virulence, and can have limited efficacy in individuals with poor mucosal health. On account of these limitations, new types of mucosal vaccine vectors are necessary. There has been increasing interest and success in developing recombinant LAB as next generation mucosal vaccine vectors due to their natural acid and bile resistance, stability at room temperature, endogenous activation of innate and adaptive immune responses, and the development of molecular techniques that allow for manipulation of their genomes. To enhance the immunogenicity of these LAB vaccines, numerous adjuvant strategies have been successfully employed. Here, we review these adjuvant strategies and their mechanisms of action which include: Toll-like receptor ligands, secretion of bacterial toxins, secretion of cytokines, direct delivery to antigen presenting cells, and enterocyte targeting. The ability to increase the immune response to LAB vaccines gives them the potential to be powerful mucosal vaccine vectors against mucosal pathogens.

Antilisterial Potential of Lactic Acid Bacteria in Eliminating Listeria monocytogenes in Host and Ready-to-Eat Food Application

“…LAB, e.g., L. paracasei subsp. paracasei NTU 101 or LAB-expressing antigen have been proved to upregulate the expression of surface proteins, e.g., CD40, CD80, CD86, and MHC class II on antigenpresenting cells (APCs) via interaction with APCs' surface peptide which activates APCs or CD154 on CD4 + T cells, providing costimulatory signaling for T cells' activation, proliferation, and differentiation to trigger costimulatory molecules and cytokines' secretion, inducing an adaptive immune response [118,125,131]. L. paracasei subsp.…”

The Role of Mucosal Immunity and Recombinant Probiotics in SARS-CoV2 Vaccine Development

“…Some microorganisms from various genera such as Leuconostoc , Lactococcus , Lactobacillu s, Pediococcus , and Streptococcus are more widespread [ 11 ]. The challenge needed to be overcome is selecting the proper vector among all LAB [ 144 ]. Choosing the relevant strains as vaccine carrier is a critical step.…”

A cross talk between the immunization and edible vaccine: Current challenges and future prospects

“…To understand the impact of adjuvant strategies on the immune response to lactic acid bacteria ( LAB ) mucosal vaccine, it's essential to explore the endogenous immune activating mechanisms possessed by LAB [ 89 , 90 ]. The features that make LAB particularly attractive to be used as mucosal vaccine vector is that it ability to stimulate innate immunity response through its Gram-positive cell wall of lipoteichoic acid and peptidoglycan that activate pattern-recognition receptors such as nucleotide-binding oligomerization domain ( NOD )-like receptor ( NLR ) family, toll-like receptor ( TLR ) 2, and C-type lectin receptors.…”

“…The features that make LAB particularly attractive to be used as mucosal vaccine vector is that it ability to stimulate innate immunity response through its Gram-positive cell wall of lipoteichoic acid and peptidoglycan that activate pattern-recognition receptors such as nucleotide-binding oligomerization domain ( NOD )-like receptor ( NLR ) family, toll-like receptor ( TLR ) 2, and C-type lectin receptors. Different LAB species can activate TLR9, TLR6, and TLR3 as well as stimulate interferon responses [ 90 ]. In addition, some LAB stains can bond to intestinal mucus and mucosal epithelium or microfold (M) cells leading to mucosal colonization and increase uptake and transport to the mucosal immune induction sites such as Peyer's patches and tonsillar crypts.…”

“…In addition, some LAB stains can bond to intestinal mucus and mucosal epithelium or microfold (M) cells leading to mucosal colonization and increase uptake and transport to the mucosal immune induction sites such as Peyer's patches and tonsillar crypts. Lactic acid bacteria can interact with APCs such as induced IgG and SIgA and dendritic cells [ 90 ]. The mechanism of activation of dendritic cells and the resulting immune response depends on the lactic acid stain.…”