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A Proof-of-Concept Rapid Diagnostic Test for Onchocerciasis: Exploring New Peptide Biomarkers and the Use of Gold Nanoshells as Novel Reporter Nanoparticles Maria J. Gonzalez-Moa, Bieke Van Dorst, Ole Lagatie, Ann Verheyen, Lieven Stuyver, and Marco A. Biamonte ACS Infect. Dis., Just Accepted Manuscript • DOI: 10.1021/acsinfecdis.8b00031 • Publication Date (Web): 16 Mar 2018 Downloaded from http://pubs.acs.org on March 17, 2018
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ACS Infectious Diseases
A Proof-of-Concept Rapid Diagnostic Test for Onchocerciasis: Exploring New Peptide Biomarkers and the Use of Gold Nanoshells as Novel Reporter Nanoparticles Maria J. Gonzalez-Moa,a Bieke Van Dorst,b Ole Lagatie,b Ann Verheyen,b Lieven Stuyver,b Marco A. Biamontea* *Corresponding Author: Marco Biamonte. e-mail:
[email protected] a
Drugs & Diagnostics for Tropical Diseases, 4898 Ronson Ct, Suite C, San Diego, CA 92111, USA
b
Janssen Diagnostics, Turnhoutseweg 30, B-2340 Beerse, Belgium
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Three O. volvulus immunogenic peptide sequences recently discovered by peptide microarray were adapted to a lateral flow assay (LFA). The LFA employs gold nanoshells as novel high-contrast reporter nanoparticles and detects a serological response against the 3 peptides, found in OvOC9384, OvOC198, and OvOC5528, respectively. When tested on 118 sera from O. volvulus infected patients and 208 control sera, the LFA was 90, 63, and 98% sensitive for each peptide, respectively, and 99–100% specific vs. samples from healthy volunteers. Samples of other filarial infections cross-reacted by 7–24%. The sensitivity, specificity, and cross-reactivity values matched those obtained by ELISA with the same sample set. While the exact choice of peptide(s) will require fine tuning, this work establishes that O. volvulus peptides identified by peptide microarray can be translated into an antibody-based LFA and that gold nanoshells provide the same sensitivity, specificity, and cross-reactivity as the corresponding ELISA assays. Keywords: Onchocerciasis, Rapid Diagnostic Test, Lateral Flow Assay, Gold, Nanoparticles, Nanoshells
Onchocerciasis, also known as river blindness, affects an estimated 15.5 million people, with 99% of the cases being found in sub-Saharan Africa.1,2 Onchocerciasis is caused by the filarial nematode Onchocerca volvulus and is transmitted by Simulium spp. blackflies which, upon a bloodmeal, inject infective larvae (L3 development stage) into a human host. The L3 larvae mature into adult worms and subsequently reproduce to release embryos called microfilariae (mf). The adults nest within subcutaneous nodules, while the mf reside in the skin.3 Upon dying, the mf cause intense inflammatory responses with manifestations ranging from pruritus (severe itching), to epilepsy, nodding syndrome, mental retardation, stunted growth, and permanent blindness.4,5 The World Health Organization (WHO) has fought onchocerciasis in Africa for nearly 30 years via mass drug administration (MDA) of ivermectin, with distribution rounds repeated yearly over 10–15 years. 2 ACS Paragon Plus Environment
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ACS Infectious Diseases
The MDA programs were originated under the Onchocerciasis Control Programme (OCP, 1989–1995) and were subsequently administered by the African Programme for Onchocerciasis Control (APOC, 1995–2017).6 They are now overseen by the Expanded Special Project for Elimination of Neglected Tropical Diseases (ESPEN, 2017–).7 As the focus shifts from controlling to eliminating onchocerciasis, new diagnostic tools able to detect minimal (0.1–1%) disease prevalence are acutely needed. The ideal device would be a rapid diagnostic test (RDT) with over 90% sensitivity to keep sample sizes reasonably small, and with over 99.9% specificity, so that the number of false positives (
