Mucosal immunity and tolerance: relevance to vaccine development

Abstract

The mucosal immune system of mammals consists of an integrated network of lymphoid cells which work in concert with innate host factors to promote host defense. Major mucosal effector immune mechanisms include secretory antibodies, largely of immunoglobulin A (IgA) isotype, cytotoxic T cells, as well as cytokines, chemokines and their receptors. Immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune system, and deliberate vaccination or natural immunization by a mucosal route can effectively induce immune suppression. The diverse compartments located in the aerodigestive and genitourinary tracts and exocrine glands communicate via preferential homing of lymphocytes and antigen-presenting cells. Mucosal administration of antigens may result in the concomitant expression of secretory immunoglobulin A (S-IgA) antibody responses in various mucosal tissues and secretions, and under certain conditions, in the suppression of immune responses. Thus, developing formulations based on efficient delivery of selected antigens/tolerogens, cytokines and adjuvants may impact on the design of future vaccines and of specific immunotherapeutic approaches against diseases associated with untoward immune responses, such as autoimmune disorders, allergic reactions, and tissue-damaging inflammatory reactions triggered by persistent microorganisms.

Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination

“…Mucosal immunity forms a first line of defense by means of secretory IgA and cytotoxic T cells against epitheliumtransmitted pathogens, and so it would seem important to develop vaccines that induce effective immune responses at mucosal barriers. Most current vaccines are administered by needle and syringe, generating effective antibody and cellmediated responses in the systemic compartment, but not in mucosal sites (4). In contrast, mucosal vaccines administered either orally or nasally have been shown to be effective in inducing antigen-specific immune responses in both systemic and mucosal compartments (5)(6)(7)(8).…”

α-Galactosylceramide Can Act As a Nasal Vaccine Adjuvant Inducing Protective Immune Responses against Viral Infection and Tumor

“…Not surprisingly then, many studies have focused on developing mucosal vaccines capable of effectively inducing both mucosal and systemic immune responses (1)(2)(3)(4). However, mucosal vaccines comprised solely of protein Ags induce only a weak immune response or tolerance.…”

Diabetes tolerogenic vaccines targeting antigen-specific inflammation

“…Only recently has the use of vaccines that induce tolerogenic immunity to suppress Keywords: antigen specific inhibition, autoimmune disease treatment, co-immunization, immuno-suppressors, immune suppression, inflammation, tolerance, suppressive vaccine, tolerogenic vaccine, type 1 diabetes host immune responses gained research momentum following the discovery of T reg cells and their suppressive functions. Although the tolerogenic vaccine concept is still in its infancy, mucosal tolerance induced by vaccination 23 and by specific immunotherapy (SIT) for allergy desensitization 24 were long ago proven effective in successful pioneering studies. Now a body of evidence is accumulating under the concept of tolerogenic vaccination.…”