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

Calderon-Quintal, J. A.; Teh-Poot, C.; Piste, L. M. P.; Martinez-Vega, P. P.; Dzul-Huchim, V.; Torres-Acosta, F.; Waleckx, E.; Villanueva-Lizama, L. E.; Ortega-Lopez, J.; Herrera, C.; Dumonteil, E.; Cruz-Chan, J. V.

doi:10.1101/2025.05.12.653529

bioRxiv · 10.1101/2025.05.12.653529

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

Calderon-Quintal, J. A.·Teh-Poot, C.·Piste, L. M. P.·Martinez-Vega, P. P.·Dzul-Huchim, V.·Torres-Acosta, F.·Waleckx, E.·Villanueva-Lizama, L. E.·Ortega-Lopez, J.·Herrera, C.·Dumonteil, E.·Cruz-Chan, J. V.

View original source ↗Export metadata ↓

Abstract

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.

Source connections

Published article ↗

Explore related subjects

microbiology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Calderon-Quintal, J. A., Teh-Poot, C., Piste, L. M. P., Martinez-Vega, P. P., Dzul-Huchim, V., Torres-Acosta, F., Waleckx, E., Villanueva-Lizama, L. E., Ortega-Lopez, J., Herrera, C., Dumonteil, E., Cruz-Chan, J. V.. 2025-05-14. Randomized field trial of a therapeutic vaccine against Trypanosoma cruzi natural infection in dogs and correlates for efficacy. https://doi.org/10.1101/2025.05.12.653529

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

A population-scale landscape of the subgingival microbiome reveals divergent routes to periodontal dysbiosis

Periodontitis is an archetypical mucosal inflammatory disease in which microbiome dysbiosis at the tooth-epithelial interface interacts with host genetic and behavioral risk factors to drive immune-mediated tissue destruction. Although subgingival microbiome compositional shifts are thought to parallel disease severity, microbiome variation at the population-level and its relationship to periodontal clinical phenotypes and disease-modifying factors remain poorly defined. Here, we use unsupervised manifold learning to map the compositional landscape of the subgingival microbiome in 1,355 adults spanning periodontal health to severe periodontitis. We identified eight latent microbiome states organized along a branching continuum from eubiosis to dysbiosis. An intermediate microbial configuration marked ecological destabilization and bifurcation into two distinct periodontitis-associated dysbiotic trajectories, distinguished by links to gingival inflammation and smoking. Although the microbiome trajectories broadly tracked periodontal destruction, a minority of individuals showed discordant microbiome-clinical phenotypes, with some individuals with periodontitis retaining otherwise eubiotic microbiomes enriched for low-abundance pathobionts, while some cases of health or mild disease had highly dysbiotic communities, suggesting distinct host susceptibility. Together, these findings define a population-scale ecological landscape of the subgingival microbiome, reveal divergent trajectories to periodontal dysbiosis, and highlight heterogeneity in the relationship between microbial community structure and clinical disease expression.

microbiology↗

bioRxiv2026

The iron-binding siderophore enterobactin is required for the response of multi-drug resistant Klebsiella pneumoniae to zinc limitation

To persist during infection Klebsiella pneumoniae must overcome nutrient iron and zinc limitation imposed by the host immune system through a process called nutritional immunity. Secreted small molecule siderophores are a major virulence determinant of Klebsiella pneumoniae pathogenesis and are presumed to overcome nutritional immunity by binding iron for bacterial acquisition. In this work, we set out to identify how a multi-drug resistant K. pneumoniae grows in zinc limited environments. Using unbiased transcriptomics, proteomics, and an arrayed transposon screen, we identified that synthesis and uptake of the siderophore enterobactin is required to allow for growth in low zinc conditions. Iron-specific chelators did not replicate this phenotype and addition of supplemental iron through heme in growth media could not complement severe growth defects of enterobactin mutant K. pneumoniae experiencing zinc limitation. Finally, zinc starvation induced enterobactin production independent of the canonical zinc uptake regulator (Zur) transcription factor suggesting an unidentified regulatory mechanism by which Gram-negative pathogens may respond to zinc stress. Together, these studies expand the role of enterobactin beyond iron regulation and highlight a previously unreported link between iron and zinc homeostasis in Klebsiella pneumoniae.

microbiology↗

bioRxiv2026

A microbiota-derived protease links phage susceptibility to host epithelial responses

Bacteriophages are major ecological drivers of gut microbial ecology, yet whether bacterial mechanisms that determine phage susceptibility have consequences for the mammalian host remains poorly understood. Here, we identify dipeptidyl peptidase 11 (Dpp11a), the predominant active serine protease of the prevalent gut commensal Phocaeicola vulgatus, as an unexpected bacterial defence factor. Dpp11a protects against environmental proteases and confers resistance to bacteriophage infection. Metatranscriptomic analyses further reveal increased expression of both dpp11a and P. vulgatus-associated phage transcripts in ulcerative colitis stool samples, indicating that both components of this interaction are transcriptionally active in disease-associated human microbiomes. Using the microfluidic gut-on-a-chip co-culture model HuMiX, we show that the absence of Dpp11 is accompanied by altered epithelial tight-junction remodelling during phage-bacterial infection. Together, our findings reveal that the consequences of bacterial phage defence can extend beyond phage-bacterium interactions to the mammalian epithelium.

microbiology↗