Periodic Reporting for period 2 - Vacc-iNTS (Advancing a GMMA-based vaccine against invasive non-typhoidal salmonellosis through Phase 1 trial in Europe and sub-Saharan Africa)
Periodo di rendicontazione: 2021-04-01 al 2022-09-30
Invasive non-typhoidal Salmonella (iNTS) infections are a serious health concern causing about 535,000 cases per year, of which more than 400,000 were in sub-Saharan Africa (sSA), where the highest incidence is observed (34.5 cases per 100,000 person-years). Commonly affecting infants, young children, and immuno-compromised adults, morbidity occurs in 20-25 % of cases. No vaccine is currently available.
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 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 aims to conduct 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 includes 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.
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 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 aims to conduct 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 includes 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.
Work performed and major achievements from the beginning of the project to the end of the first reporting period include:
• Release of vaccine lots for Phase 1
• Virtual training on the serology methods
• Development of the Clinical Trial Document Package for the Phase I clinical study in Europe and study initiation
• Development of the protocol for the Phase I Clinical Study Trial in Africa
• Readiness for serology analysis of clinical samples
• Set up of exploratory immunological analyses
• Seroepidemiology study protocols and Standard Operating Procedures (SOPs) development as well as community engagement plan (CEP), data management plan (DMP), quality management plan (QMP) and COVID-19 mitigation plan in Malawi, Burkina Faso, Ghana and Kenya.
• Ethical approvals were obtained and renowed in Malawi, Burkina Faso, Ghana
• Seroepidemiological study initiation and completion of patient's recruitment
• Peer reviewed publications on international scientific journals, reporting on nontyphoidal Salmonella invasive disease incidence systematic review and invasive disease complications and deaths
• Drafting of manuscript on literature for the Probability of Occurrence model of iNTS disease
• Drafting of manuscript on trasmission model of iNTS disease
• Training of staff in endemic countries
• Initiated the COI episode enrolment in all three countries
• Preparation of the health facility cost collection, and providing the excel-based tool and training sessions to the local teams
• Strong communication and community engagement. Upon consultations and engagements, community leaders have agreed to collaborate and approved the implementation of SAiNTS and COI-CEA studies within the broader frameworks of Salmonella sero-surveillance and Vaccine Trials
• Effective project coordination and management
• Appointment of Scientific and Ethics advisory Boards
• Consortium Agreement and Data Management Plan
• Effective dissemination and communication
• Plan for Exploitation and Dissemination of project Results update
• Project website (www.vacc-ints.eu) update and maintenance
• Twitter handle (@vacc-ints) maintenance
• Implementation of community engagement activities and training of field workers
• Community sensitization and dissemination established by all field sites
• Material Transfer Agreements developed and signed
• Successful interactions with WHO and PD-VAC committees
• Release of vaccine lots for Phase 1
• Virtual training on the serology methods
• Development of the Clinical Trial Document Package for the Phase I clinical study in Europe and study initiation
• Development of the protocol for the Phase I Clinical Study Trial in Africa
• Readiness for serology analysis of clinical samples
• Set up of exploratory immunological analyses
• Seroepidemiology study protocols and Standard Operating Procedures (SOPs) development as well as community engagement plan (CEP), data management plan (DMP), quality management plan (QMP) and COVID-19 mitigation plan in Malawi, Burkina Faso, Ghana and Kenya.
• Ethical approvals were obtained and renowed in Malawi, Burkina Faso, Ghana
• Seroepidemiological study initiation and completion of patient's recruitment
• Peer reviewed publications on international scientific journals, reporting on nontyphoidal Salmonella invasive disease incidence systematic review and invasive disease complications and deaths
• Drafting of manuscript on literature for the Probability of Occurrence model of iNTS disease
• Drafting of manuscript on trasmission model of iNTS disease
• Training of staff in endemic countries
• Initiated the COI episode enrolment in all three countries
• Preparation of the health facility cost collection, and providing the excel-based tool and training sessions to the local teams
• Strong communication and community engagement. Upon consultations and engagements, community leaders have agreed to collaborate and approved the implementation of SAiNTS and COI-CEA studies within the broader frameworks of Salmonella sero-surveillance and Vaccine Trials
• Effective project coordination and management
• Appointment of Scientific and Ethics advisory Boards
• Consortium Agreement and Data Management Plan
• Effective dissemination and communication
• Plan for Exploitation and Dissemination of project Results update
• Project website (www.vacc-ints.eu) update and maintenance
• Twitter handle (@vacc-ints) maintenance
• Implementation of community engagement activities and training of field workers
• Community sensitization and dissemination established by all field sites
• Material Transfer Agreements developed and signed
• Successful interactions with WHO and PD-VAC committees
iNTS is an important emerging bacterial neglected infectious disease of sub-Saharan Africa. There is no licensed vaccine against iNTS, and the emergence of multidrug antimicrobial resistant strains is compromising efficacy of current affordable antimicrobials. High case fatality rates, difficult diagnosis and increasing antibiotic resistance strongly advocate for rapid development of an effective vaccine.
The objective of the Vacc-iNTS project is to conduct a Phase I study to demonstrate the safety and immunogenicity of the iNTS-GMMA candidate vaccine in healthy European and African adults, and to strengthen a collaborative network of iNTS experts to raise awareness of disease burden and favor vaccine deployment in limited-resource settings.
Vacc-iNTS will undertake essential development of a vaccine for a high burden, truly neglected infectious disease of sSA using new methodology for vaccine production that is simple, low-cost and effective at inducing immune responses. Vacc-iNTS will conduct Phase I clinical trial in Europe and sSA of the iNTS-GMMA vaccine and further advance it for Phase II clinical trials. It is a long overdue intervention for a neglected disease of high importance to Africa. This effort is expected to have a significant impact in reducing disease burden and its socio-economic consequences. Furthermore, Vacc-iNTS will support the clinical development of the GMMA technology, an innovative and affordable vaccine platform suitable to tackle a range of poverty related diseases and significantly contribute to Sustainable Development Goals (SDGs) achievement. Clinical data in the target population from GMMA-based vaccines are indeed essential to define the true potential of this innovative vaccine technology. The Vacc-iNTS project will ultimately increase the number and quality of vaccine candidates for neglected infectious diseases appropriate for implementation and uptake by health systems with limited resources.
The project is significantly contributing to the recommendation, planning, implementation and uptake of the vaccine by low-income countries thanks to its multidisciplinary team of experts, contributing data and evidence at the different stages of this complex process. The partners of Vacc-iNTS will address the downstream constraints for the effective deployment and uptake by limited-resources public health systems of a novel vaccine against iNTS. Understanding the public health value of vaccines for under-recognized diseases of poverty is considered a necessary advocacy information that drives investments on vaccine development, policy, financing and uptake of vaccine in low- and middle-income countries.
Vacc-iNTS will also contribute significantly to capacity building in African by involving scientists from these institutions, providing training as well as exchanging critical information. The knowledge gained from these trainings will be necessary not only to perform the studies in the Vacc-iNTS project, but also for future collaborations.
The objective of the Vacc-iNTS project is to conduct a Phase I study to demonstrate the safety and immunogenicity of the iNTS-GMMA candidate vaccine in healthy European and African adults, and to strengthen a collaborative network of iNTS experts to raise awareness of disease burden and favor vaccine deployment in limited-resource settings.
Vacc-iNTS will undertake essential development of a vaccine for a high burden, truly neglected infectious disease of sSA using new methodology for vaccine production that is simple, low-cost and effective at inducing immune responses. Vacc-iNTS will conduct Phase I clinical trial in Europe and sSA of the iNTS-GMMA vaccine and further advance it for Phase II clinical trials. It is a long overdue intervention for a neglected disease of high importance to Africa. This effort is expected to have a significant impact in reducing disease burden and its socio-economic consequences. Furthermore, Vacc-iNTS will support the clinical development of the GMMA technology, an innovative and affordable vaccine platform suitable to tackle a range of poverty related diseases and significantly contribute to Sustainable Development Goals (SDGs) achievement. Clinical data in the target population from GMMA-based vaccines are indeed essential to define the true potential of this innovative vaccine technology. The Vacc-iNTS project will ultimately increase the number and quality of vaccine candidates for neglected infectious diseases appropriate for implementation and uptake by health systems with limited resources.
The project is significantly contributing to the recommendation, planning, implementation and uptake of the vaccine by low-income countries thanks to its multidisciplinary team of experts, contributing data and evidence at the different stages of this complex process. The partners of Vacc-iNTS will address the downstream constraints for the effective deployment and uptake by limited-resources public health systems of a novel vaccine against iNTS. Understanding the public health value of vaccines for under-recognized diseases of poverty is considered a necessary advocacy information that drives investments on vaccine development, policy, financing and uptake of vaccine in low- and middle-income countries.
Vacc-iNTS will also contribute significantly to capacity building in African by involving scientists from these institutions, providing training as well as exchanging critical information. The knowledge gained from these trainings will be necessary not only to perform the studies in the Vacc-iNTS project, but also for future collaborations.