Mucosal Vaccines: Recent Progress in Understanding the Natural Barriers

Abstract

It has long been known that protection against pathogens invading the organism via mucosal surfaces correlates better with the presence of specific antibodies in local secretions than with serum antibodies. The most effective way to induce mucosal immunity is to administer antigens directly to the mucosal surface. The development of vaccines for mucosal application requires antigen delivery systems and immunopotentiators that efficiently facilitate the presentation of the antigen to the mucosal immune system. This review provides an overview of the events within mucosal tissues that lead to protective mucosal immune responses. The understanding of those biological mechanisms, together with knowledge of the technology of vaccines and adjuvants, provides guidance on important technical aspects of mucosal vaccine design. Not being exhaustive, this review also provides information related to modern adjuvants, including polymeric delivery systems and immunopotentiators.

Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine

“…Mucosal applications of dental caries vaccines are generally preferred for the induction of sIgA antibody in the salivary compartment, since mucosal IgA immune responses are most efficiently induced by the administration of vaccines onto mucosal surfaces while injected vaccines are generally poor inducers of mucosal immunity [49]. Many investigators have shown that exposure of antigen to mucosally associated lymphoid tissue in the gut, nasal, bronchial, or rectal site can give rise to immune responses not only in the region of induction, but also in remote locations.…”

Current prospects and future challenges for nasal vaccine delivery

“…24,25 IgA has several functions in mucosal defense including the entrapment of antigens or pathogens in mucus to prevent them from direct contact with the mucosal surface. 15,26 In addition, sIgA may also block or provide steric hindrance to surfaces of pathogenic molecules that may inhibit their attachment to the epithelium. 27 The predominance of IgA in mucosal areas is a result of mutual collaboration between plasma cells and epithelial cells.…”

“…Those that have the ability to adhere to mucosal surfaces and selectively target M cells or APCs, should be the most effective. 18,26 Chitosan has been much investigated, and is a polysaccharide manufactured from chitin found in crustacean shells or fungi by a deacetylation process. Because of the range of sources this polymer is available in a range of molecular weights, but all are made up of repeating units of glucosamine and N-acetylglucosamine and bear a positive charge making it mucoadhesive.…”

“…[76][77][78] Aspects such as vaccine formulations and delivery strategies are important in designing new vaccines so that efficient induction of the innate and adaptive immune response can be obtained according to the target pathogen. 18,26 Particulate delivery systems that can imitate pathogens such as polymeric nanoparticles and liposomes are considered a promising approach for nasal vaccine delivery.…”

“…Many studies have investigated these abilities and ascribed immune boosting response to one, other or both qualities. 26 Mucosal adjuvants that have been tested for intranasal vaccine delivery including: MF59 emulsion (containing squalene oil, the surfactants Span 85 and Tween 80 and citrate buffer), 105,106 lipopolysaccharide, 84,107 TLR agonists, 41,108,109 chitosan, 110 trimethylchitosan, 91,110 bacterial outer membrane protein 111 and cholera toxin 112 or heat-labile enterotoxin (LT) from E.coli. 113 Some side effects have been found with the use of bacterial toxin when given intranasally, including Bell's palsy (Facial paralysis) and other adverse events related to disorders of the facial nerves.…”