Summary
Typhoid fever remains highly prevalent in Pakistan, spreading through contaminated food and water. In 2019, Pakistan became the first country to introduce typhoid conjugate vaccine (TCV) into its routine immunization program following an XDR typhoid outbreak in Sindh. Although TCV has reduced the disease burden, recent reports of breakthrough infections raise concerns about vaccine effectiveness and possible genetic changes in S. Typhi.
This project aims to identify underlying molecular mechanisms behind these breakthrough infections and to understand why some children do not develop adequate protection following vaccination. To investigate it further, archived serum samples, from a previously published TCV immunogenicity study, will be used to develop pooled control sera from vaccinated individuals. We will recruit TCV vaccinated children who later developed culture-confirmed typhoid fever (breakthrough cases) and their S. Typhi strains will be collected to:
1. Assess anti-Vi polysaccharide antibody titers in pooled sera of vaccinated controls through ELISA, using Vi antigens derived from breakthrough S. Typhi strains, pre-TCV era H58 isolates and reference Ty2 strain.
2. Evaluate the functional capacity of antibodies in pooled control sera through opsonophagocytic and serum bactericidal assay.
3. Genomic sequencing of S. Typhi strains from breakthrough cases to ascertain whether genetic changes particularly in Vi capsular polysaccharide contribute to immune evasion.
We seek to know whether breakthrough infections are primarily due to variability in host immune response or pathogen adaptation. Our findings will help improve vaccine design and deployment strategies and aid in reducing typhoid burden in Pakistan and our endemic countries.
Dr Junaid Iqbal
Assistant Professor
Aga Khan University
Pakistan
Collaborators:
Dr Farah Naz Qamar, The Kamruddin Mohamed Jessani Endowed Professor, Aga Khan University, Pakistan
Dr Tahir Yousafzai, Assistant Professor (Research), Aga Khan University, Pakistan
Dr Megan Carey, Research Fellow, London School of Hygiene and Tropical Medicine, UK