Language
English
Publication Date
12-15-2025
Journal
NPJ Vaccines
DOI
10.1038/s41541-025-01301-y
PMID
41397983
PMCID
PMC12714763
PubMedCentral® Posted Date
12-15-2025
PubMedCentral® Full Text Version
Post-print
Abstract
This study explored the development and evaluation of mRNA vaccine candidates targeting Schistosoma mansoni tetraspanin-2 (Sm-TSP-2). We designed constructs encoding either full-length Sm-TSP-2, or its large extracellular loop (EC2) domain in secretory, membrane-anchored, or cytosolic forms. In a murine model, the secreted and membrane-anchored versions of Sm-TSP-2-EC2 induced the highest antigen-specific antibody titers. These two construct designs, along with full-length Sm-TSP-2 mRNA, also significantly reduced adult worm and egg burden compared to controls. The membrane-anchored Sm-TSP-2-EC2 mRNA was the most effective, lowering worm and egg burdens by 66.7% and 66.9%, respectively. Protective responses induced by the mRNA vaccines were comparable to those elicited by the Sm-TSP-2-EC2 protein formulated with Alum. Histopathological analysis revealed smaller hepatic granulomas surrounding worm eggs, supporting the immunopathological benefit of vaccination. Using a systematic mRNA-based approach, we optimized the presentation of the Sm-TSP-2-EC2 and demonstrated that extracellular exposure of EC2 is essential for eliciting a protective response.
Keywords
Immunology, Microbiology
Published Open-Access
yes
Recommended Citation
de Oliveira, Athos Silva; Alwan, Sevan; LoVerde, Philip T; et al., "mRNA Vaccines Encoding Variant Forms of Sm-Tsp-2 Confer Protective Immunity Against Schistosoma mansoni" (2025). Faculty and Staff Publications. 5861.
https://digitalcommons.library.tmc.edu/baylor_docs/5861