mRNA vaccines targeting Leptospira immunoglobulin-like proteins confer partial protection in a hamster model of leptospirosis
10
Issued Date
2026-02-15
Resource Type
ISSN
0264410X
eISSN
18732518
Scopus ID
2-s2.0-105025560081
Pubmed ID
41453244
Journal Title
Vaccine
Volume
73
Rights Holder(s)
SCOPUS
Bibliographic Citation
Vaccine Vol.73 (2026)
Suggested Citation
Techawiwattanaboon T., Leekitcharoenphon R., Alameh M.G., Boonkea S., Sangkanjanavanich N., Nakornpakdee Y., Ajimathorn Y., Prompetchara E., Ketloy C., Buranapraditkun S., Palaga T., Kanthawong S., Heyes J., Weissman D., Ruxrungtham K., Patarakul K. mRNA vaccines targeting Leptospira immunoglobulin-like proteins confer partial protection in a hamster model of leptospirosis. Vaccine Vol.73 (2026). doi:10.1016/j.vaccine.2025.128099 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/114820
Title
mRNA vaccines targeting Leptospira immunoglobulin-like proteins confer partial protection in a hamster model of leptospirosis
Author's Affiliation
University of Pennsylvania
Chulalongkorn University
The Children's Hospital of Philadelphia
Penn Medicine
Khon Kaen University
Faculty of Science, Mahidol University
Faculty of Medicine, Khon Kaen University
Faculty of Medicine, Chulalongkorn University
Armed Forces Research Institute of Medical Sciences, Thailand
Genevant Sciences Corporation
Chulalongkorn University
The Children's Hospital of Philadelphia
Penn Medicine
Khon Kaen University
Faculty of Science, Mahidol University
Faculty of Medicine, Khon Kaen University
Faculty of Medicine, Chulalongkorn University
Armed Forces Research Institute of Medical Sciences, Thailand
Genevant Sciences Corporation
Corresponding Author(s)
Other Contributor(s)
Abstract
Leptospirosis is a neglected tropical disease with significant global health and economic impacts, particularly in resource-limited regions. This study reports the development of the first mRNA-based vaccines for leptospirosis, targeting the C-terminal region of LigA (LigAc) and the N-terminal region of LigB (LigBn) of Leptospira interrogans serovar Pomona. Transfection of lipid nanoparticle (LNP)-encapsulated mRNA constructs into HEK293T cells confirmed antigen expression and secretion, with proteins exhibiting higher-than-expected molecular weights due to glycosylation. In Jcl:ICR mice, LigAc- and LigBn-mRNA-LNPs elicited rapid and robust antibody responses, with significantly higher IgG titers than recombinant proteins formulated with AddaVax adjuvant. Immune sera from Lig-mRNA-LNP-vaccinated mice promoted complement-mediated killing of pathogenic leptospires in vitro. Moreover, the mRNA-LNP vaccines generated antigen-stimulated IFN-γ–ELISpot responses consistent with Th1-associated cellular activation, similar to recombinant proteins. Protective efficacy was then evaluated in golden Syrian hamsters immunized either intramuscularly or intradermally. Lig-mRNA-LNPs conferred partial protection, with a maximum survival rate of 25 % in LigBn-mRNA-LNPs vaccinated hamsters. The protective rates of Lig-mRNA-LNPs were equivalent to those of recombinant Lig protein formulations. The surviving hamsters showed reduced renal leptospiral colonization and histopathological changes, comparable to those observed in the uniformly surviving killed-leptospires group. These findings establish proof-of-concept for an mRNA vaccine platform against leptospirosis and highlight its potential application pending further optimization.