Pediatric Phase I/II age de-escalation dose finding study of a vaccine against invasive non-typhoidal salmonellosis in sub-Saharan Africa (PEDVAC-iNTS)

Invasive non-typhoidal salmonellosis (iNTS), an important overlooked poverty-related infectious disease in sub- Saharan Africa (sSA), is associated with increasing antibiotic resistance (AMR) and is classified by the World Health Organization as a high priority pathogen for developing new antibiotics.

Despite an estimated 59,100 iNTS deaths in 2017 and 14.5% case fatality rate particularly in children <5-years of age in sSA, no vaccine is currently available. Medical need, difficult diagnosis and increasing AMR strongly advocate for rapid development of an effective vaccine.

A novel vaccine, based on the highly cost-effective GMMA-technology, currently being developed by GSK Biologicals and GSK Vaccines Institute for Global Health, includes outer membrane exosomes released by genetically modified Salmonella enterica serovars Typhimurium and Enteritidis, the most common causative agents of African iNTS.

Clinical proof-of-concept for GMMA-technology was achieved with a Shigella sonnei vaccine in European and African adults.

In animals, 2-component iNTS-GMMA vaccine has induced potent bactericidal antibodies and protection in bacterial challenge murine model. Simple, robust and scalable manufacturing processes for iNTS-GMMA vaccine, suited for sSA, have been developed.

PEDVAC-iNTS primary goal is to advance clinical development of the vaccine for use in the target population (i.e., infants in sSA) by conducting a pediatric PhaseI/II study in a sSA country with high medical need.

The study builds on the efforts undertaken within Vacc-iNTS EC H2020 funded project, investigating safety and immunogenicity of the iNTS-GMMA vaccine in healthy European adults. PEDVAC-iNTS will evaluate additional lots of the vaccine using an age de-escalation and dose escalation approach.

Firstly, it will assess safety, in small cohorts of Ghanaian adults, children and infants, and subsequently define the optimal vaccine dose for further development, in a larger number of infants. Serological and transcriptomic analyses will be conducted to profile the vaccine immune response.

Additionally, antimicrobial susceptibility of iNTS-causing Salmonella strains, isolated in Ghana, will be evaluated to further enhance the database of AMR pathogens in sSA.

In addition to the clinical development goal, PEDVAC-iNTS plans to develop a collaborative network of experts from academia, industry and non-profit organizations including partners from endemic countries in sSA.

The network will generate data to accelerate vaccine development and enhance disease awareness in resource- limited endemic countries where iNTS disease is causing a significant public health burden.

Finally, the project aims to establish the necessary advocacy and outreach to global and regional policy and decision makers to address the necessary preconditions for successful vaccine implementation.