OUR APPROACH
Strategy
The SHIGETECVAX consortium aims at advancing a vaccine candidate (ShigETEC) developed by Eveliqure Biotechnologies that is radically different from other previous and current Shigella/ETEC vaccine efforts.
Figure 3: Antibody responses against Shigella antigens. (A) The genus Shigella is differentiated into four species:
S. dysenteriae (15 serotypes); S. flexneri (19 serotypes); S. boydii (19 serotypes); and S. sonnei (1 serotype). (A) The serotype-specific O-polysaccharide antigen is associated with the lipopolysaccharide (LPS) on the bacteria’s surface (coat) and is highly variable due to species differences. So far, most approaches to vaccine development have attempted to induce protection against the LPS (5).
(B) Removal of the coat in ShigETEC vaccine allows to generate a robust immune response against conserved antigens, leading to the development of cross-protective immunity.
Instead of targeting the immunodominant, but highly variable Shigella LPS O-antigen, elimination of this antigen in this vaccine candidate allows for the immune recognition of minor and highly conserved antigens that are shared among different types of Shigella and ETEC (Figure 3). In addition, ShigETEC expresses a tandem repeat of a fusion protein of LTB and an ST toxoid that induces neutralizing antibodies and thus protective immunity against both toxins of ETEC strains. The vaccine has been rendered non-invasive by inactivation of the type III secretion system. A third deletion inactivates a putative enterotoxin in order to further improve the safety profile of the vaccine strain (more information https://www.eveliqure.com/how-it-works).
(5) Walker RI, Wierzba TF, Mani S, Bourgeois AL (2017) Vaccines against Shigella and enterotoxigenic Escherichia coli: A summary of the 2016 VASE Conference. Vaccine 35(49 Pt A):6775-6782.