A review of vaccine development and research for industry animals in Korea

Lee, Nak-Hyung; Lee, Jung-Ah; Park, Seung-Yong; Song, Chang-Seon; Choi, In-Soo; Lee, Joong-Bok

A number of species of live bacteria have been used for vaccine carriers that enable the delivery of cloned vaccine antigen enterically or intransally. For enteric bacteria, most of them are species with the ability to colonize intestinal mucosa, in particular, mucosa-associated lymphoid tissue, which is the main point of invasion of enteric bacteria [36, 48] . However, the reality of application for this type of vaccine is complicated and less efficient due to low level of expression of the inserted protein, and the antigen is less efficiently translocated on the surface of bacteria, where most protective antigens are displayed [48] . In addition, the immune response of clone antigen is often much weaker than the response to carrier protein of origin. Another issue is that the level of immune response to the carrier may preclude its future use either for displaying or for delivering foreign proteins. For this purpose, the bacterial genes responsible for virulence, colonization, survival, and modulation of gene expression should be deleted in vivo. It is desirable to remove independent genes or genetic loci that contribute to virulence in order to assure the attenuation of the bacterial carrier by reducing the possibility of reversion [36] . Another strategy is to create mutants that have been chemically altered. The Ty21a strain of Salmonella was derived in the fashion and licensed for preventing typhoid fever. The goal of creating a carrier vector is to present foreign antigen to immune system in the context of a live bacterial infection so that the host immune system recognizes the antigen as a natural-form immunogen and thereby develops a broader immunity to corresponding pathogen. The antigen expressed in a carrier vector is transported to the cell surface to stimulate antibody production into the cytoplasmic pathway where elicit cytotoxic T lymphocyte response. However, the majority of bacteria do not infect cells, and the recombinant antigen should be expressed at the bacterial surface, where the peptide would elicit the production of antibody. The engineered enteric pathogen is the most commonly used for this purpose, so that they can induce mucosal immunity against foreign polypeptide upon oral delivery. In the field of live bacteria vectors, an attenuated Salmonella carrier as an oral delivery vector has been used for malaria, http://www.ecevr.org/ http://dx. doi.org/10.7774/cevr.2012.1.1.18 anthrax, and cholera. The challenging issue for creating carrier vaccines is that a vaccine strain should retain the sufficient ability of replication in the gut and be attenuated enough not to be pathogenic, however, have its ability of expression of appropriate level of foreign proteins. Interestingly, the ability of certain bacteria to replicate intracellularly may augment the ability of expressed foreign peptide within the cells and consequently elicit cellular immunity to the corresponding pathogen. Attenuated Salmonella can cross the intestinal wall and deliver expressed antigen through activation pathway of innate immunity to the intestinal immune tissues. Another vector strain has employed commensal bacteria for presentation of foreign antigens, since the strains are naturally colonized without inducing clinical signs and are able to persist for years in body compartments [59] .