Project description
A pioneering vaccine for diarrhoea may accomplish what predecessors could not
Diarrhoea is typically a non-threatening nuisance in western civilisations but it is a killer in developing countries, particularly for children under five years of age. In cases where children do survive, malnourishment due to poverty is augmented by dehydration and severe undernutrition as a result of infection. This can have long-term effects on physical and cognitive development. SHIGETECVAX is developing a novel oral vaccine against two closely related bacteria that are leading causes of diarrhoea. Based on antigens not targeted in previous vaccines, it is much safer, enabling higher doses. Potentially more effective against both pathogens, this vaccine could save millions of lives.
Objective
Although vaccination is an effective way to reduce the huge disease burden associated with diarrhoea caused by enteric pathogens, many attempts to develop vaccines for shigellosis and ETEC infections have failed and a number of current approaches are too complex and costly to provide an adequate solution for LMICs. This Consortium is dedicated to advancing a radically new approach against Shigella and ETEC based not on the immunodominant, but highly variable Shigella LPS O-antigen, target of almost all past and current vaccine development efforts. There are four pillars on which the ShigETEC vaccine has been designed: (i) Elimination of the LPS O-antigen to allow recognition of multiple antigens on the cell surface that are shared among different serotypes of Shigella and are increasingly being recognized as important in protection from shigellosis. These antigens are also closely related to those of ETEC and may also help in protecting against that pathogen as well. (ii) Elimination of the invasiveness of Shigella by disruption of the invasion complex resulting in a much safer/less reactogenic oral vaccine that can take advantage of gut mucosal immunity, possibly allowing administration of high vaccine doses and therefore addresses the low immunogenicity seen with other live attenuated vaccine candidates. (iii) Addition of detoxified toxin antigens of ETEC that will induce neutralizing/blocking antibodies to these critical virulence factors. (iv) Rational molecular design of ShigETEC will allow future generations of vaccines to include additional antigens for other pathogens. The work programme entails manufacture of clinical trial material, first-in-human testing for safety and immunogenicity in non-endemic adults, a sero-epidemiology study to learn about natural immune response to the vaccine, and importantly testing the vaccine in endemic populations. The Consortium comprises partners from EU and Bangladesh that bring along highly complementary expertise.
Fields of science
Programme(s)
Funding Scheme
RIA - Research and Innovation actionCoordinator
69115 Heidelberg
Germany