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.
Highlights
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)
We review the current strategies being investigated to adjuvant the immune response to mucosal delivered LAB vaccine vectors. As these studies are reviewed, it is important to recognize that the adjuvant effect on the immune response may be altered by the mucosal route of administration, genus and species of LAB used as the delivery vehicle, the antigen per se, and the mechanism of antigen display
To understand the effect that adjuvant strategies have on the immune response to a LAB mucosal vaccine, it is important to review the endogenous immune activating mechanisms possessed by LAB
Summary
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). It is likely that despite the endogenous immune activating properties of LAB, one or multiple adjuvant strategies may be necessary to induce robust and long lasting protective immune responses This may be especially true if the vaccine is expressing poorly immunogenic antigens or is used in sensitive populations such as individuals who are immune suppressed, nutrient compromised, have an altered microbiome, or have an increased mucosal disease burden. We review the current strategies being investigated to adjuvant the immune response to mucosal delivered LAB vaccine vectors As these studies are reviewed, it is important to recognize that the adjuvant effect on the immune response may be altered by the mucosal route of administration (intranasal, oral, or intravaginal), genus and species of LAB used as the delivery vehicle, the antigen per se, and the mechanism of antigen display (secreted, surface-display, or intracellular). Careful study and selection of each of these variables will likely be necessary to develop optimized LAB mucosal vaccines
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