Research and Development

Diarrheal Diseases – The Medical Problem

Travelers' diarrhea (TD) is the most common illness affecting travelers and military personnel deployed to endemic countries. The very same diseases caused by the same pathogens are leading causes of death in children living in resource-poor part of the world.

ETEC and Shigella, the two leading bacterial causes of diarrhea

ETEC (Enterotoxigenic E. coli) is a bacterium that colonizes the small intestine and causes severe watery diarrhea, abdominal cramps, and fever. ETEC infections are potentially life threatening in young children living in resource poor countries due to significant fluid loss and severe dehydration.

Shigella is an aggressive pathogen that invades and destroys the cells lining the large intestine, causing mucosal inflammation, ulceration and bloody diarrhea (bacillary dysentery). The bacteria are highly infectious, and as few as 10 to 100 microorganisms are sufficient to cause disease. The genus Shigella includes four species and according to their variations, the species are further divided into 47 serotypes. Infection by one given serotype does not result in protection against other strains – which is one of the main reasons of many failed vaccine attempts.

ETEC and Shigella, the two leading bacterial causes of diarrhea account for about 50% of the 2.2 billion cases annually. Each year millions of children are hospitalized and approximately 1.5 million die from severe, dehydrating diarrhea and dysentery in low-resource countries. Estimates suggest that ETEC and Shigella are responsible for the deaths of approximately 500,000 to up to 1 million deaths among children under the age of five each year.

Prevention through vaccination

Due to dehydration, not appropriate medical care and increasing rate of resistance to the most commonly used antibiotics, diarrhea is very difficult to manage. For all of these reasons, prevention through vaccination is a critical part of the strategy to reduce the incidence and severity of diarrheal diseases. There are licensed vaccines developed against typhoid, cholera (Dukoral) and recently to rotavirus (Rotarix, Rotashield). Unfortunately, however, no vaccines are available to prevent Shigella or ETEC infections.

The EveliQure Technology

Live attenuated Shigella strains developed so far are invasive and afford serotype-dependent protection. In contrast, the proprietary EveliQure vaccine technology platform is based on a live, genetically attenuated Shigella vaccine strain able to induce broad protection against shigellosis.

The platform is amenable for the heterologous expression of diarrheal antigens and therefore can provide protective immunity against multiple pathogens. The first product candidate, Shigetec™ expresses ETEC antigens known to induce protective immunity against ETEC infections when expressed in appropriate forms.

The vaccine will be administered orally in a liquid form, and expected to induce mucosal immune response that is necessary to prevent enteral infections.