Description du projet
Des bactéries conçues pour produire des vaccins contre la salmonellose invasive non typhoïde
La salmonellose invasive non typhoïde (INTS) est un problème majeur de santé publique, particulièrement en Afrique subsaharienne où elle tue davantage que la fièvre typhoïde. Affectant fréquemment les nourrissons, les jeunes enfants et les adultes immunodéprimés, la morbidité survient dans 20 à 25 % des cas. Les vaccins sont désespérément nécessaires ici. Le projet Vacc-iNTS, financé par l’UE, a utilisé une nouvelle méthodologie de production de vaccins simple, peu coûteuse et très efficace pour induire une réponse immunitaire dans le corps. Ils vont le tester au cours d’essais cliniques de phase 1 et planifient déjà la collecte de données pour soutenir les activités des phases 2 et 3.
Objectif
Invasive non-typhoidal Salmonellosis (iNTS) is an important emerging Neglected Infectious Disease in resource-poor settings of sub-Saharan Africa (sSA). No vaccine is currently available. Estimated 263,000 iNTS deaths per year in <5 year olds, a 20% case fatality rate, difficult diagnosis and increasing antibiotic resistance strongly advocate for rapid development of an effective vaccine. Vacc-iNTS bridges the gap between preclinical and early clinical development of a novel vaccine against iNTS, based on GMMA (Generalized Modules for Membrane Antigens) from the most common African iNTS serotypes (Typhimurium and Enteritidis). The highly cost-effective GMMA-technology, developed by partner 2, is based on outer membrane blebs released by genetically modified bacteria. Clinical proof-of-concept for the GMMA-technology was achieved with a Shigella sonnei vaccine in European and African adults. In animals, iNTS-GMMA were highly immunogenic and induced antibodies with bactericidal activity against African iNTS strains. Simple, robust and scalable manufacturing processes for iNTS-GMMA, suited for sSA, have been developed. Vacc-iNTS proposes GMP manufacturing of clinical lots followed by a two-stage Phase 1 trial in healthy European and African adults to investigate safety and immunogenicity of the iNTS-GMMA vaccine. Analysis include serum antibody levels and functionality, cellular responses, transcriptomics and data integration through a systems biology approach. Sero-epidemiological analysis will be conducted to provide essential data for future Phase 2 and 3 trials. Vacc-iNTS will also strengthen a collaborative network of iNTS experts from academia, industry and non-profit including partners from disease-endemic countries of sSA. The network will generate data to accelerate further vaccine development, enhance awareness, drive advocacy and vaccine deployment in limited-resources disease-endemic countries, tackling major roadblocks in advancing a vaccine against iNTS.
Champ scientifique
- engineering and technologymechanical engineeringmanufacturing engineering
- natural sciencesbiological sciencesmicrobiologybacteriology
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsvaccines
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Mots‑clés
Programme(s)
Régime de financement
RIA - Research and Innovation actionCoordinateur
53100 Siena
Italie