Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles

Abstract

Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production.

Immunomodulatory Properties of Bacterium-Like Particles Obtained From Immunobiotic Lactobacilli: Prospects for Their Use as Mucosal Adjuvants

“…The use of mucosal vaccines triggers local and systemic responses limiting the pathogens at the site of entry, reducing their replication in epithelial cells, the alteration of the epithelial barrier, and the action of toxins on the mucosa. In addition, mucosal vaccination helps preventing the spread of the pathogen to internal tissues and to the environment (17,18). Despite the several advantages of mucosal vaccination, it faces many difficulties including poor immunogenicity at low concentrations, chemical and enzymatic degradation, potential toxicity, and the risk of generating tolerance rather than protective immunity (17,19).…”

“…In addition, mucosal vaccination helps preventing the spread of the pathogen to internal tissues and to the environment (17,18). Despite the several advantages of mucosal vaccination, it faces many difficulties including poor immunogenicity at low concentrations, chemical and enzymatic degradation, potential toxicity, and the risk of generating tolerance rather than protective immunity (17,19). In this work, we demonstrated that IBLP derived from highly efficient immunomodulatory lactobacilli are an interesting alternative as mucosal adjuvants.…”

“…There is a growing need for the development of new and improved mucosal vaccines to diminish the morbidity and mortality associated to infectious diseases, particularly against those targeting the respiratory and gastrointestinal tracts (17,18). The search and characterization of mucosal adjuvants to enhance the immunity against antigens is of fundamental importance to advance in this path.…”

Immunogenic Properties of Lactobacillus plantarum Producing Surface-Displayed Mycobacterium tuberculosis Antigens

“…On the other hand, when it comes to L. plantarum, the oral route is of interest, because this food-grade bacterium is a natural resident of the intestinal microflora (48,49). Mucosal immunization is potentially highly advantageous in vaccinology since the majority of pathogens enter the body via mucosal surfaces and it has been established that mucosal vaccination generates both mucosal and systemic immune protection (47,50).…”

Rational Design and In Vivo Characterization of Vaccine Adjuvants

“…12 The functionality and development of both delivery systems and immunostimulators as adjuvants are reviewed elsewhere. 6,[13][14][15][16][17][18][19] Aluminum-based adjuvants have been extensively used in human vaccines for almost a century, and for most of that period no other adjuvants were approved for human use. 20 The adjuvant effects of aluminum-based adjuvants were empirically discovered, while the exact mechanisms of action have remained relatively obscure until recently.…”