Characterisation of Mucosal Secretory IgA Responses to Salmonella Typhimurium Infection

Summary 

Non-typhoidal Salmonellae are a group of bacteria that typically cause diarrhoeal disease (dNTS). This group of bacteria are particularly harmful to individuals who are HIV-positive, malaria-infected, or malnourished in sub-Saharan Africa. In these individuals, the bacteria can spread throughout the body and cause a more severe illness known as invasive non-typhoidal Salmonella (iNTS). There is a growing interest in developing vaccines to prevent iNTS, particularly with the rise of antibiotic-resistant infections, and several vaccines are in early-stage development.

To develop effective vaccines, we need to better understand the way the immune system protects against NTS infection. Secretory IgA (sIgA) is a type of common mucosal antibody known to provide protection against some intestinal (gut) bacteria. Compared with other bacteria, the role of sIgA in preventing NTS infection in humans has been relatively understudied. 

Our research project aims to develop and validate a way to measure sIgA targeted at Salmonella Typhimurium (STm) in stool and saliva samples. We aim to do this by standardised enzyme-linked immunosorbent assay (ELISA) to measure sIgA against STm. We then aim to use this to measure the strength, durability and targets of the sIgA response in healthy volunteers challenged with STm and individuals exposed to STm in a high-burden setting. These will be linked with antibody measures in blood to see how closely they are related.  We propose to use these methods in future vaccine studies to better understand immunity to STm and NTS.