Tu169 - Evaluation of an mRNA Vaccine for Dirofilariasis in Dogs

Tanmayee Vagesna – Microbiology and Immunology – University of Illinois; Camar Ameril, MS – Fulbright Visiting Student Researcher, Biomedical Sciences, University of Illinois; Justin Richner, PhD – Assistant Professor, Microbiology and Immunology, University of Illinois; Ramaswamy Kalyanasundaram, DVM, PhD – Professor, Biomedical Sciences, University of Illinois

Abstract Text: Dirofilariasis is a disease of canines caused mainly by the filarial nematode Dirofilaria immitis. Our laboratory developed a recombinant protein vaccine for lymphatic filariasis disease, which is also caused by a filarial parasite B. malayi. The genomes of D.immitis and B.malayi was compared and it showed significant similarity of over 88%. The three major vaccine candidates of B. malayi, the heat shock protein 12.6 (HSP), thioredoxin peroxidase-2 (TPX) and abundant larval transcript (ALT-2) showed 97%, 96% and 93% sequence similarity respectively. In this study, we evaluated the potential of rBmHAXT as a prophylactic vaccine for D. immitis. Recent advances in the mRNA vaccine field, especially during the Covid-19 pandemic provided an exciting opportunity for developing an mRNA vaccine for other infectious diseases including parasitic infections. Thus, in this project, we constructed two different mRNA formulation, one the tetravalent (HAXT) mRNA and the second a mixture of all four antigens (H+A+X+T) as an mRNA vaccine for D. immitis. Initial ELISA and confocal microscopy studies confirmed that the dog cell line, Madin-Darby Canine Kidney (MDCK) cells can express and secrete HAXT protein following transfection with HAXT DNA. Subsequently, mice were immunized three times with the mRNA vaccine, and challenged with D. immitis L3 larvae. Our results showed that the mRNA vaccine induced significantly high titer of IgG antibodies compared to controls. Challenge study results are awaited. Preliminary studies showed that the mRNA immunization induces significant protective immunity. The mRNA vaccination also generated significant antigen-specific central memory T cells in mice.