Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines

Criscuolo, E.; Caputo, V.; Diotti, R. A.; Sautto, G. A.; Kirchenbaum, G. A.; Clementi, N.

Many LAB, in particular, Lactobacillus spp and Bacillus subtilis, were used in preclinical studies against different infectious diseases. Different results have been obtained from these studies, but an elicited immune response was observed in all of them. As an example, the production of high levels of specific IgA and systemic IgG after immunization with bacillus spores expressing toxin A peptide repeat was reported [80] , while in another paper, L. lactis expressing HEV antigen ORF2 vaccine was tested and a specific Th2-based cellmediated immune response was revealed as well as the production of specific mucosal IgA and serum IgG [81] . Another study reported a Th1/Th2 immune response elicited after the immunization with Csenolase-expressing Bacillus subtilis [82] . Another example is the oral administration of B. subtilis spores expressing urease B of Helicobacter pylori that provide protection against Helicobacter infection [83] . An important feature of LAB is their natural adjuvanticity and their immunomodulatory effects, although the molecular mechanism of these capabilities is not completely understood [84] . Moreover, other studies reported an effect on dendritic cell maturation and an induction of cytokine secretion [85, 86] . Despite the promising characteristics of recombinant LAB as mucosal vaccine vectors and given the encouraging results from murine studies, some aspects need to be taken into consideration, namely, the fact that vaccine strains cannot be considered avirulent, even if it could be listed as GRAS, due to potential transfer of antibiotic selection markers among microbes [78, 87] . Furthermore, other factors are important for the development of LAB-based vaccines. As an example, the necessity of a suitable delivery system since different administration routes produce different immune effects. Additionally, the role of specific adjuvants and the correct localization (intracellularly or on the bacterial surface) of each expressed antigen need consideration [88] . Overall, additional studies and clinical trials are needed for the development of efficient vaccines based on LAB.