Advancing the understanding of cell mediated immunity to natural Shigella infection through functional immunological approaches

Summary 

Shigellosis remains one of the leading bacterial aetiologies of diarrhoea associated mortality and morbidity globally. One third of these deaths occur in children under the age of 5 and the burden is significantly high in low-and middle-income countries such as Malawi. Vaccination against shigellosis is one practical means of lessening disease burden in endemic settings and yet no licenced Shigella vaccines are available to date. Several promising candidate vaccines are being evaluated at different stages of preclinical and clinical development. Comprehensive understanding of host immune responses to Shigella through robust and well-established immunological assays is pivotal to accelerate shigella vaccine development. Whilst significant advances are underway towards unravelling correlates of protection against shigella, fewer studies have dissected the role of T cell mediated Immunity in naturally exposed individuals in an African context.

Successful evaluation of T cell mediated immunity against Shigella will complement efforts aimed at deciphering correlates of protection to natural and potential shigella vaccine candidates.

We plan to conduct functional assays to dissect the role of T cell mediated immunity against Shigella in a potentially disease burdened setting (Malawi) by leveraging archived blood samples collected from a well-established diarrhoea surveillance (Diasurv) platform. Findings from this project has several important implications including advancing our knowledge on T cell mediated immunity to Shigella which is a rarely investigated and yet equally important component of adaptive immune system. In addition, this work will complement the ongoing Shigella serology underway in Malawi whilst also building in-country capacity and expertise in readiness for future vaccine trials.