Measuring non-typhoidal Salmonella specific antibodies in oral fluid as a non-invasive alternative to serum

Dr Sean Elias, Post-Doctoral Scientist
University of Oxford (UK)
Dr Joesph Campo 200x200px
Dr Esther Muthumbi, KEMRI-Wellcome (Kenya) 
Professor Cal MacLennan, University of Oxford (UK)  

Immunoepidemiological studies from Africa support the concept that antibody acquisition with age likely provides protection against invasive non-typhoidal Salmonella disease. Induction of antibodies to key antigenic targets such as the O antigen of lipopolysaccharide has been a significant target for vaccine development. Whilst pre-clinical studies in animals have shown promise for such vaccines, in humans we a lack a true correlate of protection.  It would be valuable to better understand antibody induction to non-typhoidal Salmonella antigens to help develop an effective vaccine for all individuals.

Most studies of invasive non-typhoidal Salmonella disease tend to revolve around young children who, along with HIV and malaria-infected individuals are amongst the most susceptible to infection. Measuring antibody titres in such individuals is usually performed using serum samples. Particularly in young children, obtaining serum through venepuncture can be stressful to both child and parent. As a result, patient retention or recruitment of healthy subjects can be difficult as parental consent is often withdrawn once their child is healthy or is not given in the first place.

We propose to explore the use of non-invasive methods of measuring antibody responses to non-typhoidal Salmonella to increase patient acceptability and seek to identify comparable signatures to serum-derived antibody responses. Oral-fluid antibody has been successfully measured as an alternative to serum for a number of bacterial and viral antigens and the two responses have often correlated strongly. This alternative method may also provide additional data to support new correlates of protection, susceptibility or carriage, given Salmonella is an orally-ingested pathogen and this is a measure of a relevant mucosal response. This study will compare antibody responses across different age groups in both Kenya and the UK.