Abstract
BackgroundThe lack of suitable diagnostic tools contributes to the high prevalence of tuberculosis (TB) worldwide. Serological tests, based on multiple target antigens, represent an attractive option for diagnosis of this disease due to their rapidity, convenience, and low cost.MethodsMeasures to reduce non-specific reactions and thereby improve the specificity of serological tests were investigated, including blocking antibodies against common bacteria in serum samples and synthesizing polypeptides covering non-conserved dominant B-cell epitopes of antigens. In addition, a fusion polyprotein containing HspX and eight other antigen sequences was constructed and expressed to increase overall sensitivity of the tests.ResultsInclusion of Escherichia coli lysate partially increased the specificity of the serological tests, while synthesis and inclusion of peptides containing non-conserved sequences of TB antigens as well as dominant B-cell epitopes reduced non-specific reactions without a decrease in sensitivity of the tests. A polyprotein fusing HspX and eight other antigen sequences was constructed and displayed 60.2% sensitivity, which was higher than that of HspX and the other individual antigen segments. Moreover, the specificity of the polyprotein was 93.8%, which was not significantly decreased when compared with HspX and the other individual antigen segments.ConclusionsThe roles of the fusion polyprotein in the humoral immune response against TB infection were demonstrated and provide a potential novel approach for the development of TB diagnostics.
Highlights
Tuberculosis (TB) is one of the most prevalent infectious diseases and among the top 10 causes of death worldwide despite substantial progress toward TB control over the last decades
The serum samples were pre-adsorbed with Escherichia coli and other bacterial lysates, including V. mimicus, S. aureus, B. subtilis, P. vulgaris, S. epidermidis, Enterobacter aerogenes, and S. citreus, to block antibodies against antigens from these bacteria
The value of serum samples from strong false positive (SFP) and weak false positive (WFP) markedly decreased after preadsorption with P. vulgaris, Enterobacter aerogenes, and Escherichia coli compared with groups without any bacteria lysates
Summary
Tuberculosis (TB) is one of the most prevalent infectious diseases and among the top 10 causes of death worldwide despite substantial progress toward TB control over the last decades. A rapid, accurate, and cost-effective diagnostic tool for TB is urgently required to control this disease. The sensitivities and specificities of the currently available options based on single or multiple target antigens for TB are variable and do not yet meet the requirements for clinical use. In 2011, the World Health Organization (WHO) issued a policy recommendation against the use of the various commercial serological tests for TB diagnosis due to the suboptimal sensitivity and specificity [9]. Serological tests, based on multiple target antigens, represent an attractive option for diagnosis of this disease due to their rapidity, convenience, and low cost
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