Advancing a GMMA-based vaccine against invasive non-typhoidal salmonellosis through Phase I trial in Europe and sub-Saharan Africa

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 proofof- 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 nonprofit 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 diseaseendemic countries, tackling major roadblocks in advancing a vaccine against iNTS.

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 proofof- 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 nonprofit 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 diseaseendemic countries, tackling major roadblocks in advancing a vaccine against iNTS.