Descrizione del progetto
Un vaccino pionieristico per la diarrea potrebbe realizzare ciò che i predecessori non hanno potuto
La diarrea è tipicamente un disturbo per niente minaccioso nelle civiltà occidentali, ma è mortale nei paesi in via di sviluppo, in particolare per i bambini di età inferiore ai cinque anni. Nei casi in cui i bambini riescono a sopravvivere, la malnutrizione dovuta alla povertà viene aggravata dalla disidratazione e dalla grave denutrizione a seguito dell’infezione. Tutto questo può avere effetti a lungo termine sullo sviluppo fisico e cognitivo. Il progetto SHIGETECVAX sta sviluppando un nuovo vaccino orale contro due batteri strettamente correlati che rappresentano le principali cause di diarrea. Basato su antigeni non mirati nei precedenti vaccini, questo è molto più sicuro, consentendo dosi più elevate. Potenzialmente più efficace contro entrambi i patogeni, questo vaccino potrebbe salvare milioni di vite.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Invito a presentare proposte
Vedi altri progetti per questo bandoBando secondario
H2020-SC1-2018-Two-Stage-RTD
Meccanismo di finanziamento
RIA - Research and Innovation actionCoordinatore
69115 Heidelberg
Germania