Title: Seroepidemiology in Africa for iNTS vaccine (SAiNTS)
Funder: Wellcome Trust

Abstract: Invasive non-typhoidal Salmonella (iNTS) is estimated to cause 535,000 illnesses, 77,500 deaths, and the loss of 4,263,500 disability-adjusted life years (DALY’s) every year, with 86.7% of the global burden falling in sub-Saharan Africa (sSA). The proposed SAiNTS study will work with the EU-funded Vacc-iNTS consortium, and will complete a comprehensive rural community-based seroepidemiological study in a malarial area, measuring age-stratified exposure, susceptibility and natural immunity to NTS, and leveraging multiple additional cohort datasets, with the overarching goals of: &bull; Accelerating the clinical development of 3 new iNTS vaccines in early clinical development through phase 1 and phase 2a immunogenicity studies &bull; Providing a model contributing to realistic assessments of the impact of iNTS vaccination in varying epidemiological settings across Africa. The SAiNTS study, accordingly, has the following specific aims: Aim 1: Develop a regression model for age-dependant, naturally acquired immunity against iNTS disease (&alpha;LPS-IgG antibody and SBA) and compare to the age-stratified incidence of Salmonella enteric infections (eNTS). Aim 2: Estimate a Correlate of Protection for invasive NTS, based on naturally acquired antibody levels and known age-stratified disease incidence. Aim 3: Assess the effect of different iNTS risk factors on the age-dependent acquisition of natural immunity, and how they might impact on estimated correlates of protection and iNTS vaccine impact in different scenarios.

Lay abstract: Invasive non-typhoidal Salmonella (iNTS) is estimated to cause 535,000 illnesses, 77,500 deaths, and the loss of 4,263,500 disability-adjusted life years (DALY’s) every year, with 86.7% of the global burden falling in sub-Saharan Africa (sSA). The proposed SAiNTS study is a comprehensive rural community-based sero-epidemiological study in a malarial area, measuring age-stratified exposure, susceptibility and natural immunity to NTS, and leveraging multiple additional cohort datasets, with the overarching goals of: • Accelerating the clinical development of 3 new iNTS vaccines in early clinical development through phase 1 and phase 2a immunogenicity studies • Providing a model contributing to realistic assessments of the impact of iNTS vaccination in varying epidemiological settings across Africa. The SAiNTS study, accordingly, has the following specific aims: Aim 1: Develop a regression model for age-dependant, naturally acquired immunity against iNTS disease (&alpha;LPS-IgG antibody and SBA) and compare to the age-stratified incidence of Salmonella enteric infections (eNTS). Aim 2: Estimate a Correlate of Protection for invasive NTS, based on naturally acquired antibody levels and known age-stratified disease incidence. Aim 3: Assess the effect of different iNTS risk factors on the age-dependent acquisition of natural immunity, and how they might impact on estimated correlates of protection and iNTS vaccine impact in different scenarios. Aim 4: Explore the effect of malaria vaccination on the development of natural immunity to NTS, and the potential impact on iNTS disease.

Research activity codes: 3.4 VACCINES
Health categories: INFECTION