Feasibility of Anti-Idiotypic Aptamers to Detect Rickettsia Exposure
Feasibility of Anti-Idiotypic Aptamers to Detect Rickettsia Exposure
John G. Bruno
ABSTRACT
Twenty-seven DNA aptamers were developed against the Fab fragments of murine antibodies developed to bind Rickettsia rickettsii and Rickettsia typhi. A feasibility study was conducted to generate anti-idiotypic aptamers against Fab fragments of these antibodies and to determine if the aptamers were capable of emulating rickettsial antigens to enable sensitive detection of rickettsia exposure in humans who have seroconverted. Such anti-idiotypic aptamer antigens might also serve as rickettsial vaccines, if fully developed. The top five highest affinity R. rickettsii and top five R. typhi anti-Fab aptamers as assessed by enzyme-linked aptamer sorbent assay (ELASA) screening were shown to specifically bind their cognate antibodies when captured by their Fc tails on the surface of Protein A-conjugated magnetic beads. While no clear similarities in the partial or complete primary DNA sequences or secondary stem-loop structures of these aptamers were observed, 3-dimensional computer models of these top ten anti-idiotypic aptamer candidates showed some topological similarities which suggest common binding motifs. Unfortunately, without knowledge of the hypervariable region amino acid sequences of the target antibodies, no docking simulations are possible to test this topological hypothesis, but the present work illustrates feasibility of the approach and paves the way for more sophisticated analysis that could lead to improved rickettsial serodiagnostics and aptamer-based vaccines.
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