Exploiting cholera vaccines as a versatile antigen delivery platform

Abstract

The development of safe, immunogenic and protective cholera vaccine candidates makes possible their use as a versatile antigen delivery platform. Foreign antigens can be delivered to the immune system with cholera vaccines by expressing heterologous antigens in live attenuated vectors, as fusion proteins with cholera toxin subunits combined with inactivated Vibrio cholerae whole cells or by exposing them on the surface of V. cholerae ghosts. Progress in our understanding of the genes expressed by V. cholerae during infection creates unprecedented opportunities to develop an improved generation of vaccine vectors to induce immune protection against a broad range of pathogenic organisms.

Use of Genetically Modified Bacteria to Modulate Adaptive Immunity

“…Antigens derived form lysosomal degradation (8) will be loaded on MHC-II molecules to be presented to CD4 + helper T cells (9). Alternatively, antigens leaking from phagolysosomal compartments, phagocytic endosomes or delivered directly into the cytoplasm can be processed by the proteasome (11) to be loaded on MHC-I molecules (12) for antigen presentation to CD8 + Cytotoxic T cells (13). Antigens encoded by DNA delivered by bacteria (10) may access the cell gene expression machinery after lysosomal degradation (7).…”

“…For instance, live attenuated BCG (attenuated Mycobacterium bovis), Salmonella typhi and Vibrio cholerae, are worldwide used as vaccines against tuberculosis, typhoid fever and cholera, respectively [9]. Currently, we know that the use of whole attenuated bacteria vaccines is advantageous because they can: 1. elicit strong immune responses against a variety of antigens [10][11][12], 2. retain the capacity to induce tissue-specific and favorably *Address correspondence to these authors at the Millennium Nucleus on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile. Alameda #340, Santiago 8331010, Chile; Tel: 56-2-686-2842; Fax: 56-2-686-2185; E-mail: akalergis@bio.puc.cl, kalergis@vtr.net and sbueno@bio.puc.cl skewed immune responses [13,14], 3. be significantly more affordable for mass coverage than are vaccines based on isolated or recombinant purified molecules.…”

Characterization of Antigenic Determinants in ApxIIA Exotoxin Capable of Inducing Protective Immunity toActinobacillus pleuropneumoniaeChallenge

“…The B subunits of these toxins bind with particularly high affinity to the GM1 ganglioside which is expressed on the surfaces of intestinal epithelial and M cells (Freytag and Clements, 2005;Silva et al, 2008). However, there is a limit to the size of antigen that will allow the pentamer formation of the toxin B subunit to adhere to its target site (Spangler, 1992;Liljeqvist et al, 1997;Harakuni et al, 2005).…”

Oral administration of recombinant Mycobacterium smegmatis expressing a tripeptide construct derived from endogenous and microbial antigens prevents atherosclerosis in ApoE−/− mice

“…Live vaccines obviate the need for large‐scale purification of recombinant protein, and can act as natural adjuvants . Several bacterial species including salmonella, streptococci, lactococci, vibrio Mycobacterium bovis (BCG), and Mycobacterium smegmatis have been used to deliver heterologous proteins. Mycobacterium smegmatis is a nonpathogenic fast‐growing commensal organism in humans .…”