PATH’s Center for Vaccine Innovation and Access

ETEC and Shigella

Promising new tools in the fight against diarrhea

Photo: PATH/Mike Wang

Photo: PATH/Mike Wang

Diarrhea continues to be a deadly disease for many children in the world. Poor sanitation, insufficient water treatment systems, and lack of access to appropriate medical care and vaccines translate into more than half a million deaths every year among children younger than five years, with millions more hospitalized from severe, dehydrating diarrhea.

Vaccines to prevent diarrheal diseases are an essential and lifesaving part of control strategies. These vaccines even have the potential to reduce malnutrition and developmental delays associated with severe diarrhea in children. For these reasons, PATH is developing new vaccines against the leading causes of this serious disease—rotavirus, enterotoxigenic Escherichia coli (ETEC), and Shigella.

ETEC and Shigella account for at least one billion cases of diarrhea annually. Insufficient data exist, but conservative estimates suggest that these two bacteria are responsible for more than 15 percent of child deaths from diarrhea and for many deaths in older age groups. Currently, there are no licensed vaccines against either pathogen.

To accelerate the development of safe, effective, and affordable vaccines against ETEC and Shigella for children in low-resource settings, we are working with private- and public-sector partners to pursue a number of promising vaccine approaches and related research.

A broad portfolio of vaccine candidates

We are pursuing a wide range of promising ETEC and Shigella vaccine approaches, with the goal of identifying at least one vaccine candidate for each pathogen to prioritize for late-stage development. Our portfolio includes killed whole-cell, live attenuated, and subunit vaccine candidates. We’re also assessing manufacturing partners, mostly in emerging countries, to take on the eventual manufacture and distribution of these new vaccines.

One of our most advanced candidates is a tetravalent, inactivated whole-cell ETEC vaccine called ETVAX, which we are developing in collaboration with the University of Gothenburg and Scandinavian BioPharma in Sweden. We are currently testing ETVAX in combination with the double-mutant heat-labile toxin (dmLT) adjuvant to potentially facilitate dose sparing, in a descending-age study in Bangladesh. Our next step with ETVAX/dmLT is to test the vaccine/adjuvant in combination with a formalin-inactivated, trivalent whole-cell Shigella vaccine candidate.

A combined ETEC/Shigella vaccine could be more attractive to low-resource countries for several reasons. Such a vaccine could potentially maximize impact by protecting against multiple pathogens with one vaccine, reduce delivery barriers related to cold chain and logistics, and minimize vaccine administrations in an already-crowded immunization schedule.

Innovative research to support vaccine development

We are also conducting an array of supporting research to inform and enhance our vaccine development efforts. This work includes studying innovative formulation and delivery options to make these vaccines more practical for use among children in low-resource settings, exploring new approaches to vaccine development based on systems biology, and supporting the development of controlled human infection models for enteric diseases. In support of that science informing policy, we also conduct advocacy to prioritize diarrheal disease within the broader public health arena.

Additional resources