Papers by Innocent Kadwala
BioTech
Nontyphoidal Salmonella (NTS) is a leading cause of morbidity and mortality caused by enteric pat... more Nontyphoidal Salmonella (NTS) is a leading cause of morbidity and mortality caused by enteric pathogens worldwide in both children and adults, and vaccines are not yet available. The measurement of antigen-specific antibodies in the sera of vaccinated or convalescent individuals is crucial to understand the incidence of disease and the immunogenicity of vaccine candidates. A solid and standardized assay used to determine the level of specific anti-antigens IgG is therefore of paramount importance. In this work, we presented the characterization of a customized enzyme-linked immunosorbent assay (ELISA) with continuous readouts and a standardized definition of EU/mL. We assessed various performance parameters: standard curve accuracy, dilutional linearity, intermediate precision, specificity, limits of blanks, and quantification. The simplicity of the assay, its high sensitivity and specificity coupled with its low cost and the use of basic consumables and instruments without the need...
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JCI Insight, 2020
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Proceedings of the National Academy of Sciences, 2020
Significance Nontyphoidal Salmonella serotypes are a common cause of self-limiting diarrhoeal ill... more Significance Nontyphoidal Salmonella serotypes are a common cause of self-limiting diarrhoeal illnesses in healthy adults. However, recently, a highly invasive multidrug resistant Salmonella Typhimurium sequence type 313 has emerged as a major cause of morbidity and mortality in sub-Saharan Africa, particularly in children and immunosuppressed individuals. In this paper we describe escape from MAIT cell recognition as an additional mechanism of immune evasion of S. Typhimurium ST313. As MAIT cells represent an early defense mechanism against pathogens at mucosal surfaces, and their frequency and function are altered in immunosuppressed individuals in sub-Saharan Africa, harnessing their function may offer an important therapeutic strategy to improve mucosal immunity.
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Mucosal-associated invariant T (MAIT) cells are a subset of innate T lymphocytes activated by bac... more Mucosal-associated invariant T (MAIT) cells are a subset of innate T lymphocytes activated by bacteria that produce vitamin B2 metabolites. Mouse models of infection have demonstrated a role for MAIT cells in antimicrobial defence. However, proposed protective roles of MAIT cells in human infections remain unproven and clinical conditions associated with a selective absence of MAIT cells have not been identified. We report that typhoidal and non-typhoidal S. enterica strains generally activate MAIT cells. However, African invasive disease-associated multidrug-resistant S. Typhimurium sequence type 313 lineage 2 strains escape MAIT cell recognition through overexpression of ribB, a bacterial gene that encodes the 4-dihydroxy-2-butanone 4-phosphate synthase enzyme of the riboflavin biosynthetic pathway. This MAIT cell-specific phenotype did not extend to other innate lymphocytes. We propose that ribB overexpression is an evolved trait that facilitates evasion from immune recognition b...
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Methods and Protocols
Salmonella Typhimurium and Salmonella Enteritidis are leading causative agents of invasive nontyp... more Salmonella Typhimurium and Salmonella Enteritidis are leading causative agents of invasive nontyphoidal Salmonella (iNTS) disease, which represents one of the major causes of death and morbidity in sub-Saharan Africa, still partially underestimated. Large sero-epidemiological studies are necessary to unravel the burden of disease and guide the introduction of vaccines that are not yet available. Even if no correlate of protection has been determined so far for iNTS, the evaluation of complement-mediated functionality of antibodies generated towards natural infection or elicited upon vaccination may represent a big step towards this achievement. Here we present the setup and the intra-laboratory characterization in terms of repeatability, intermediate precision, linearity, and specificity of a high-throughput luminescence-based serum bactericidal assay (L-SBA). This method could be useful to perform sero-epidemiological studies across iNTS endemic countries and for evaluation of anti...
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Papers by Innocent Kadwala