Mucosal Vaccination and Therapy with Genetically Modified Lactic Acid Bacteria

Abstract

Lactic acid bacteria (LAB) have proved to be effective mucosal delivery vehicles that overcome the problem of delivering functional proteins to the mucosal tissues. By the intranasal route, both live and killed LAB vaccine strains have been shown to elicit mucosal and systemic immune responses that afford protection against infectious challenges. To be effective via oral administration, frequent dosing over several weeks is required but new targeting and adjuvant strategies have clearly demonstrated the potential to increase the immunogenicity and protective immunity of LAB vaccines. Oral administration of Lactococcus lactis has been shown to induce antigen-specific oral tolerance (OT) to secreted recombinant antigens. LAB delivery is more efficient at inducing OT than the purified antigen, thus avoiding the need for purification of large quantities of antigen. This approach holds promise for new therapeutic interventions in allergies and antigen-induced autoimmune diseases. Several clinical and research reports demonstrate considerable progress in the application of genetically modified L. lactis for the treatment of inflammatory bowel disease (IBD). New medical targets are on the horizon, and the approval by several health authorities and biosafety committees of a containment system for a genetically modified L. lactis that secretes Il-10 should pave the way for new LAB delivery applications in the future.

Surface Display of N-Terminally Anchored Invasin by Lactobacillus plantarum Activates NF-κB in Monocytes

“…The mucosal surfaces represent the major portal of entry for pathogens, and it has been shown that it is possible to induce both systemic and mucosal immune responses via these surfaces (5). Promising results have been obtained with mucosal delivery of vaccine antigens through the intranasal, oral, or genital mucosal surfaces by both commensal and attenuated pathogenic bacteria (62). There has been much focus on vaccine delivery by attenuated pathogenic bacteria because of their intrinsic immunostimulatory properties, but such strains could potentially regain their virulence and, also, confer a risk to immunocompromised individuals (18).…”

“…Still, the use of nonpathogenic bacteria such as L. plantarum in immunization strategies usually does not result in complete protection against the disease, suggesting that vaccine adjuvants are needed to boost the immune response generated by the antigen-expressing bacteria (62). Early studies with LAB have shown that both systemic and mucosal immune responses improve substantially upon coexpression of adjuvants, such as interleukin-12 (IL-12) and IL-6, with an antigen (4,60).…”

Construction and Immunological Evaluation of Dual Cell Surface Display of HIV-1 Gag and Salmonella enterica Serovar Typhimurium FliC in Lactobacillus acidophilus for Vaccine Delivery

“…Many previous studies have demonstrated that commensal microbes carrying antigens can confer protective immunity (39,40). For example, recombinant Lactococcus lactis expressing the HIV type 1 (HIV-1) V2-V4 loop of Env induced antigen-specific immune responses that protected mice from challenge with recombinant vaccinia virus carrying the HIV env gene (41).…”

Bioengineered probiotics, a strategic approach to control enteric infections

“…51,52 Over the last decade recombinant probiotics have been generated for mucosal delivery of therapeutic and prophylactic molecules including DNA, peptides, single-chain variable fragments, cytokines, enzymes, and allergens. 53,54 The major advantages of probiotic bacteria as delivery system are their (1) ability to colonize mucosal surface, (2) tolerance to gastric acid and bile salts enabling survival and transit through the gastrointestinal tract (GIT), and (3) sustained colonization and prolonged protection against pathogen. 53,55 Furthermore, oral recombinant probiotics offer several advantages: direct delivery of active molecule to the mucosal surface without the need for bio-separation of the active molecules, increased shelf-life and stability, low delivery costs, and ease of technology transfer following prototype development.…”

“…53,54 The major advantages of probiotic bacteria as delivery system are their (1) ability to colonize mucosal surface, (2) tolerance to gastric acid and bile salts enabling survival and transit through the gastrointestinal tract (GIT), and (3) sustained colonization and prolonged protection against pathogen. 53,55 Furthermore, oral recombinant probiotics offer several advantages: direct delivery of active molecule to the mucosal surface without the need for bio-separation of the active molecules, increased shelf-life and stability, low delivery costs, and ease of technology transfer following prototype development. This led to the concept of "biodrug" that is based on the oral administration of live recombinant microorganisms for the prevention and treatment of various diseases.…”