SAL-O5_Asses the variation in lipopolysaccharide structure in circulating African invasive Salmonella Typhimuriun isolates to predict vaccine coverage

Sandra Van Puyvelde

Dr Sandra Van Puyvelde
Postdoctoral Research Fellow 
Vaccine and Infectious Diseases Institute (VAXINFECTIO), University of Antwerp (Belgium)

Collaborators:

Dr Francesca Micoli, GSK Vaccines Institute for Global Health (Italy)
Professor Calman MacLennan, Jenner Institute, University of Oxford (UK)
Professor Jan Jacobs, Clinical Sciences Department, Institute of Tropical Medicine Antwerp (Belgium)
Dr Neil Ravenscroft, University of Cape Town (South Africa)
Dr Paola Cescutti, University of Trieste (Italy)
Professor Octavie Lunguya, National Institute for Biomedical Research (INRB), Kinshasa (Democratic Republic of the Congo)

Summary

In sub-Saharan Africa, invasive non-typhoidal Salmonella (iNTS) is the major cause of bacterial bloodstream infections among young children and disease management is jeopardised by increasing antimicrobial resistance (AMR). The O-antigen portion of Salmonella lipopolysaccharide (LPS) is recognised as key target antigen for protective immunity and O-antigen-based vaccines covering the main serovars Salmonella Typhimurium and Enteritidis are in development. Some of the vaccine candidates are about to enter phase 1 clinical trials; however, efficacy in Africa will not be tested for several years. 

O-antigen structural variability can have an impact on the protective immunity of corresponding vaccines. Serotyping and genomic investigation of recent iNTS isolates from the Democratic Republic of the Congo (DRC) have shown increasing rates of iNTS isolates with variation in O-antigen structure. In particular, more than 45 % of the recent Salmonella Typhimurium isolates do not present O:5 specificity, associated to O-antigen O-acetylation. 

In this project, we will analyse the genomic variation of O-antigen of Salmonella Typhimurium DRC isolates within the African context. The genomic basis of differences in O-antigenic structure will be proven by mutagenesis experiments. We will determine the O-antigen structure from a panel of Salmonella Typhimurium isolates recently collected in DRC, ascertaining the nature of the O-antigen genomic variations. The coverage of current O-antigen based vaccines against iNTS is likely to be impacted by the O-antigen structural variability, and this project will yield key insights on how to improve the current vaccines.