Molecular Definition Of Filarial And Related Nonfilarial Genes And Proteins

National Institute Of Allergy And Infectious Diseases

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Abstract

To understand the basis of the molecular diagnostic tools that we developed and rely on highly repeated elements in the genomes of parasites, and with technological advancements to facilitate telomere-to-telomere genomes, we constructed new chromosome level reference genome assemblies for Loa loa, Strongyloides stercoralis, Baylisascaris procyonis and Dracunculus medinensis. Based on the new reference genome for Loa loa, the qPCR target LL2643 appears to be concentrated in the telomeric regions A set of potential biomarkers to complement the existing Wb123 assay for detecting human lymphatic filariasis were identified based on comparative genomic analyses. Based on the proteomic or transcriptomic evidence 12 of the proteins were shortlisted, of which Wb4 and Wb5 were the most promising targets. Quantitative immunoassays for these biomarkers for both filarial parasites have been developed and validated. The use of these biomarkers are the basis for patent (U.S Provisional Patent Application PCT/US2023/067703). The identification of tissue specific expressed proteins in B. malayi resulted in the identification of LAD2 and UDP-glucuronyltransferase as potential targets of treatment and or therapeutic interventions. Having identified BmIL-5Rbp and shown its ability to act as a human IL5 antagonist, we next were able to show that can be used therapeutically to dramatically reduce eosinophil-mediated allergic lung inflammation in mouse models (HDM and/or Ascaris infection) when administered intranasally