Kannan, J. | Search bioRxiv

bioRxiv2026

Efficacy of rDiHAVO as a potential vaccine antigen against heartworm infections in a mouse model

Dirofilariasis, or heartworm disease, is a life-threatening parasitic infection caused by the nematode parasite Dirofilaria immitis. Mosquito vectors in tropical and subtropical regions transmit the infection. Current treatment options are expensive, have a short-term effect, and depend on anthelminthic therapy. There are no licensed vaccines available for preventing heartworm infections. The primary goal of this study was to identify potential vaccine candidates, develop a tetravalent fusion protein (rDiHAVO) vaccine antigen, and evaluate its immunogenicity and efficacy in a mouse model of D. immitis infection. Results show that the rDiHAVO is highly immunogenic in mice and confers over 95% protection against a challenge infection. These findings suggest that rDiHAVO is a potential vaccine candidate against Dirofilariasis. Additional testing in dogs can advance this vaccine candidate to clinical trials.

immunology↗

bioRxiv2025

Massively parallel reporter assays identify functional enhancer variants at QT interval GWAS loci

Genome-wide association studies (GWAS) have identified >30 loci with multiple common noncoding variants explaining interindividual electrocardiographic QT interval (QTi) variation. Of the many types of noncoding functional elements, here we sought to identify transcriptional enhancers with sequence variation and their cognate transcription factors (TFs) that alter the expression of proximal cardiac genes to affect QTi variation. We used massively parallel reporter assays (MPRA) in mouse cardiomyocyte HL-1 cells to screen for functional enhancer variants among 1,018 QTi-associated GWAS variants that overlap candidate cardiac enhancers across 31 loci. We identified 445 GWAS variant-containing enhancers of which 79 showed significant allelic difference in enhancer activity across 21 GWAS loci, with multiple enhancer variants per locus. Of these, we predicted differential binding by cardiac TFs, including AP-1, ATF-1, GATA2, MEF2, NKX2.5, SRF and TBX5 which are known to play key roles in development and homeostasis, at 49 enhancer variants. Finally, we used expression quantitative trait locus mapping and predicted promoter-enhancer contacts to identify 14 candidate target genes through analyses of 36 enhancer variants at 16 loci. This study provides strong evidence for 14 cardiac genes, 10 of them novel, impacting on QTi variation, beyond explaining observed genetic associations.

genetics↗