Biology subjects

Waleckx, E.

Publications and source records attributed to Waleckx, E..

3 recordsLinked to original sources

bioRxiv2025

Randomized field trial of a therapeutic vaccine against Trypanosoma cruzi natural infection in dogs and correlates for efficacy

Background and AimsChagas disease, caused by Trypanosoma cruzi, is a vector-borne parasitic disease, with dogs acting as a major domestic host of the parasite. An immunotherapeutic vaccine would be an excellent tool to treat infections and prevent chronic cardiac disease in this host. Building on previous pre-clinical studies, we performed here the first randomized field trial of a vaccine against T. cruzi among client-owned dogs with natural infections. MethodsA total of 31 dogs with T. cruzi infection with diverse parasite strains were enrolled and received three doses of a vaccine composed of Tc24-C4 and TSA1-C4 recombinant proteins with MPLA (N=16) or saline control (N=15) and followed for up to six months to assess efficacy. ResultsBlood parasite burden and electrocardiographic (ECG) recordings as primary outcomes showed that therapeutic vaccination led to a significant decrease in parasite burden, prevented/stopped cardiac alterations and was safe. This clinical benefit was mediated by major changes in T cell activation and T cell receptor (TCR) repertoire, while antibody responses were minimally affected. In addition, vaccination also reprogrammed the ongoing trained immunity to reduce inflammation, suggesting a complex interplay between innate and T cells in its mechanism of action. ConclusionsThese results provide a strong support for the further development of a veterinary vaccine based on these antigens as well as a human therapeutic vaccine to prevent the progression of chronic cardiac disease from T. cruzi infection. Structured graphical abstractO_ST_ABSKey questionC_ST_ABSCan an immunotherapeutic vaccine against Trypanosoma cruzi control an ongoing infection and prevent the progression of chronic cardiac disease in naturally infected dogs? Key findingTherapeutic vaccination of chronically infected dogs led to a reduced blood parasite burden and prevented the progression of chronic cardiac disease (Primary outcomes). Correlates of vaccine efficacy included major changes in T cell repertoire/activation and changes in innate immunity to reduce inflammation. Take home messageImmunotherapeutic vaccination of dogs with natural infection with T. cruzi was safe and effective to control an ongoing infection with a broad diversity of parasite strains and prevented the progression of chronic cardiac disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/653529v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@17ce572org.highwire.dtl.DTLVardef@bba649org.highwire.dtl.DTLVardef@1a20405org.highwire.dtl.DTLVardef@1b61c7e_HPS_FORMAT_FIGEXP M_FIG C_FIG Translational perspectiveCurrent drug treatments for Chagas disease have major limitations due to significant adverse effects and a limited efficacy as chronic cardiac disease develops. A veterinary vaccine for dogs, a major domestic host of the parasite, would help reduce domestic transmission and improve dog health, as well as provide support for the development of a human immunotherapeutic vaccine to prevent the progression of chronic Chagasic cardiomyopathy.

microbiology↗

bioRxiv2024

mbctools: A User-Friendly Metabarcoding and Cross-Platform Pipeline for Analyzing Multiple Amplicon Sequencing Data across a Large Diversity of Organisms

We developed a python package called mbctools, designed to offer a cross-platform tool for processing amplicon data from various organisms in the context of metabarcoding studies. It can handle the most common tasks in metabarcoding pipelines such as paired-end merging, primer trimming, quality filtering, sequence denoising, zero-radius operational taxonomic unit (ZOTU) filtering, and has the capability to process multiple genetic markers simultaneously. mbctools is a menu-driven program that eliminates the need for expertise in command-line skills and ensures documentation of each analysis for reproducibility purposes. The software, designed to run in a console, offers an interactive experience, guided by keyboard inputs, assisting users along the way through data processing and hiding the complexity of command lines by letting them concentrate on selecting parameters to apply in each step of the process. In our workflow, VSEARCH is utilized for processing fastq files derived from amplicon-based Next-Generation Sequencing data. This software is a versatile open-source tool for processing amplicon sequences, offering advantages such as high speed, efficient memory usage, and the ability to handle large datasets. It provides functions for various tasks such as dereplication, clustering, chimera detection, and taxonomic assignment. VSEARCH is thus very efficient in retrieving the overall diversity of a sample. To adapt to the diversity of projects in metabarcoding, we facilitate the reprocessing of datasets with the possibility to adjust parameters. mbctools can also be launched in a headless mode, making it suited for integration into pipelines running on High-Performance Computing environments. mbctools is available at https://github.com/GuilhemSempere/mbctools, https://pypi.org/project/mbctools/.

bioinformatics↗

bioRxiv2018

Estimating the current burden of Chagas disease in Mexico: a systematic review of epidemiological surveys from 2006 to 2017

BackgroundIn Mexico, estimates of Chagas disease prevalence and burden vary widely. Updating surveillance data is therefore an important priority to ensure that Chagas disease does not remain a barrier to the development of Mexicos most vulnerable populations.\n\nMethodology/Principal FindingsThe aim of this systematic review was to analyze the literature on epidemiological surveys to estimate Chagas disease prevalence and burden in Mexico, during the period 2006 to 2017. A total of 2,764 articles were screened and 38 were retained for the final analysis. Epidemiological surveys have been performed in most of Mexico, but with variable geographic coverage. Based on studies reporting confirmed cases, i.e. using at least 2 serological tests, the national seroprevalence of Trypanosoma cruzi infection was 2.26% [95% Confidence Interval (CI) 2.12-2.41], suggesting that there are 2.71 million cases in Mexico. Studies focused on pregnant women, which may transmit the parasite to their newborn during pregnancy, reported a seroprevalence of 1.00% [95% CI 0.87-1.14], suggesting that there are 22,930 births from T. cruzi infected pregnant women per year, and 1,445 cases of congenitally infected newborns per year. Children under 18 years had a seropositivity rate of 1.49% [95% CI 1.20-1.85], which indicate ongoing transmission. Finally, cases of T. cruzi infection in blood donors have also been reported in most states, with a national seroprevalence of 0.51% [95% CI 0.49-0.53].\n\nConclusions/SignificanceOur analysis suggests a disease burden for T. cruzi infection higher than previously recognized, highlighting the urgency of establishing Chagas disease surveillance and control as a key national public health priority in Mexico, to ensure that it does not remain a major barrier to the economic and social development of the countrys most vulnerable populations.\n\nAuthor summaryIn Mexico, estimates of Chagas disease prevalence and burden vary widely due to the ecology and epidemiology of this disease resulting of many geographical, ecological, biological, and social interactions. Better data are thus urgently needed to help develop appropriate public health programs for disease control and patient care. In this study we analyzed published data on T. cruzi seroprevalence infection in Mexico between 2006 and 2017. This systematic review shows a national seroprevalence of T. cruzi infection of 2.26% [95%CI 2.12-2.41], with over 2.71 million cases in Mexico, which is higher than previously recognized. The presence of T. cruzi infection in specific subpopulations such as pregnant women, children and blood donors also informs on specific risks of infection and call for the implementation of well-established control interventions. This work confirms the place of Mexico as the country with the largest number of cases, highlighting the urgency of establishing Chagas disease control as a key national public health priority.

epidemiology↗