Plasmodium vivax malaria research has yet to fully benefit from advances in genomic surveillance that have revolutionized P. falciparum epidemiology. Closing this gap will enable monitoring the spread of drug resistance, classifying infections as local or imported, and distinguishing reinfection, recrudescence, and relapse. To achieve these objectives, microhaplotype marker panels that allow powerful genotyping of polyclonal infections are needed.MethodsWe designed a globally applicable amplicon panel for P. vivax (PvGAP), selecting targets based on both genetic diversity and distance to maximize discriminatory capability between geographic regions. We evaluated this panel with field samples from Ethiopia and in silico using whole genomes from the MalariaGEN Pv4 database.ResultsPvGAP has 80 high-diversity targets suitable for population genomics and 8 targets of epidemiological interest, such as putative markers of drug resistance. We demonstrate robust amplification with field data and competitive accuracy for relatedness inference in 3 disparate geographic regions.ConclusionsPvGAP joins existing P. vivax panels as a cost-effective and practical option for genomic epidemiology of this neglected disease. It will support drug resistance surveillance and discrimination of local and imported cases, and it may aid in separating reinfection, recrudescence, and relapse in therapeutic efficacy studies, all critical needs of National Malaria Control Programs.

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Elimination of Plasmodium vivax is challenging due to the dormant liver stages (hypnozoites), which can reactivate weeks or months after the primary infection, causing relapses and ongoing parasite transmission. Despite these challenges, P. vivax clinical case numbers have declined over the past decade in Cambodia. We used parasite genotyping to assess whether declines in reported case numbers were accompanied by changes in parasite diversity and relatedness among symptomatic infections.MethodsGenotyping was conducted on 296 symptomatic P. vivax isolates collected in eastern Cambodia in 2014, 2015, 2019, 2021, 2022, and 2023. A panel of 93 microhaplotype markers (vivaxGEN panel) was genotyped using Illumina. Population genetic measures were applied to determine infection diversity and relatedness (identity-by-descent [IBD]) each year.ResultsA total of 289 (20–94 per year) samples were successfully genotyped. The percentage of polyclonal infections was 5% in 2023 compared to 29%–55% in earlier years (P < .05). The cases collected in 2023 also had the highest proportion of infections with IBD >0.95 with 1 or more other infections (81.4% vs 0%–22.3% in 2014–2022). In contrast, cases in 2022 showed higher frequencies of polyclonal infections (55%) and increased population diversity.ConclusionsOur findings illustrate the potential of microhaplotype genotyping to characterize temporal changes in the genetic composition of symptomatic P. vivax infections and to complement conventional epidemiological surveillance.

An evolutionary model of clonal hematopoiesis (CH) describes the genetic changes of HSCs through life, predicts the ubiquity of polyclonal competition, and identifies multistage CH progression with va...

AbstractAntigen interference from residual antigen peptides is a persistent challenge in antipeptide immunocapture liquid chromatography–tandem mass spectrometry (IC-LC–MS/MS) assays, particularly when quantifying low-abundance protein biomarkers. Traditionally, carrier protein-conjugated surrogate peptides identical to those used in LC–MS/MS quantification are employed as antigens for immunization, often resulting in varying degrees of antigen interference from the resulting antipeptide polyclonal antibodies (pAbs). While precapture purification and other mitigation strategies can reduce interference, they may be insufficient for ultrasensitive antipeptide IC-LC–MS/MS assays. Here, for the first time, we demonstrate the use of carrier-protein-conjugated, stable isotopically labeled surrogate peptides as antigens for immunization. This strategy ensures that residual antigen peptide is distinguishable from endogenous analytes by mass spectrometry, effectively eliminating antigen interference. This paper details the design principles for stable isotopically labeled surrogate peptides used in antigen preparation and compares the performance of pAbs generated using labeled versus traditional nonlabeled peptide antigens. Results from over 20 batches of antipeptide pAbs demonstrate that this method enables the routine generation of antigen interference-free antipeptide pAbs, facilitating the development of ultrasensitive antipeptide IC-LC–MS/MS assays for low-abundance protein biomarker quantification without incurring additional time and significant cost. Data are available via ProteomeXchange with an identifier of PXD076272.

The Melbourne-based polyclonal antibody company reported 6% revenue growth and a A$1.4m profit improvement while advancing IMM-529 towards a Phase 2

Single-molecule DNA&nbsp;sequencing identifies recurrent somatic mutations in autoimmune B cells that may allow them to escape peripheral tolerance and cause autoimmune disease.

Here, we present a reproducible Seurat-based protocol to analyze PBMC CD4⁺ T-cell single-cell RNA sequencing data across malaria reinfection timepoints. This protocol demonstrates a reproducible Seurat-based workflow for analyzing PBMC CD4⁺ T-cell scRNA-seq data across malaria reinfection timepoints, using representative publicly available datasets to demonstrate its application: a Plasmodium-specific TCR-transgenic CD4⁺ T-cell dataset (GSE233703) and a polyclonal CD4⁺ T-cell dataset comparing...

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