Abstract

Background: Forty adult volunteers were recruited to a study f Salmonella Typhi (S. Typhi) infection in human volunteers. To etermine the host response to infection, participants received a .Typhi challenge dose of 1-5×103 or 1-5×104 colony forming nits (CFU). The antibody secreting cell (ASC) response in infected ndividuals was studied to characterise the development of immuity following infection. Methods: An enzyme-linked immunospot (ELISpot) assay was eveloped as a quantitative method to characterise the IgG, IgM nd IgA response to S. Typhi O (LPS), capsular (Vi) and flagellar (H) ntigens. Quantification was performed at baseline (day 0), day 7 nd day 10 post challenge, and 48hours following typhoid diagosis (defined by bacteraemia or a persistent raised temperature). pot forming cellswerequantifiedandarepresented as thenumber f antibody secreting cells per 106 PBMCs. Results: Secretion of typhoid antigen-specific IgG, IgM and IgA romPBMCswas detected by ELISpot on day 7 and day 10 following hallenge with S. Typhi. The results demonstrate a 6, 8 and 18-fold ncrease in specific ASC responses to O, Vi and H antigen respecively at the point of diagnosis of typhoid in individuals who met he case definition. Conclusion: We describe a rapid ELISpot method for detectng typhoid antigen-specific B cell responses. The data acquired rom study of these volunteers indicates the development of strong mmune responses to important surface antigens of S. Typhi, in hose who develop enteric fever.

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