ShigETEC – toward a solution for Shigella/ETEC diarrhoea
The proprietary Eveliqure vaccine technology platform is based on a live attenuated Shigella vaccine strain able to induce broad protection against shigellosis due to targeted genetic mutations. Previous attempts to develop a live attenuated Shigella vaccine have failed as they are invasive and only afforded serotype-dependent protection. One non-invasive Shigella vaccine was developed in the 1960s, although it was not pursued for wide commercialisation. The Eveliqure platform is amenable for the heterologous expression of diarrheal antigens and therefore can provide protective immunity against multiple pathogens.
Eveliqure’s first product, ShigETEC is an orally administered vaccine that induces broad protection against Shigella in a serotype-independent fashion and additionally against ETEC, two major pathogens responsible for diarrhoeal diseases. Based on extensive preclinical data generated by Eveliqure over the last 5 years, it has the potential to be a best-in-class diarrhoea vaccine that targets both travelers and populations in low- and middle-income countries.
Previous attempts at Shigella vaccine development have been shown to be effective: In 1961, a non-invasive Shigella flexneri 2a strain had been isolated and extensively studied. This strain, T32-ISTRATI, was shown to lack of virulence in the Serény test (keratoconjunctivitis in Guinea pigs) following serial in vitro passage (Meitert et al, 1982). A vaccine strain was developed and produced by the Cantacuzino Romanian national institute for vaccine production (Cantacuzino Institute) in Bucharest, Romania under the trade name VADIZEN. The vaccine was evaluated in the late 1960s through the 1980s in more than 65.000 individuals in Romania and China, including children, administered in multiple oral doses of 1x109 to 2x1011 CFU per dose. This vaccine was safe, well tolerated, immunogenic and protective (Meitert et al, 1984). The non-invasive phenotype of the VADIZEN vaccine was later determined to be due to the spontaneous deletion of a large portion of the invasion plasmid, including the genes ipaB and ipaC (Venkatesan et al, 1991).