Version 1
: Received: 16 September 2024 / Approved: 17 September 2024 / Online: 17 September 2024 (14:51:19 CEST)
How to cite:
Pacini, M. F.; Bulfoni Balbi, C.; Dinatale, B.; Farre, C.; Cacik, P.; Gonzalez, F. B.; Marcipar, I.; Pérez, A. R. Intranasal Trans-Sialidase Vaccine Mitigates Acute and Chronic Pathology in a Preclinical Oral Chagas Disease Model. Preprints2024, 2024091328. https://doi.org/10.20944/preprints202409.1328.v1
Pacini, M. F.; Bulfoni Balbi, C.; Dinatale, B.; Farre, C.; Cacik, P.; Gonzalez, F. B.; Marcipar, I.; Pérez, A. R. Intranasal Trans-Sialidase Vaccine Mitigates Acute and Chronic Pathology in a Preclinical Oral Chagas Disease Model. Preprints 2024, 2024091328. https://doi.org/10.20944/preprints202409.1328.v1
Pacini, M. F.; Bulfoni Balbi, C.; Dinatale, B.; Farre, C.; Cacik, P.; Gonzalez, F. B.; Marcipar, I.; Pérez, A. R. Intranasal Trans-Sialidase Vaccine Mitigates Acute and Chronic Pathology in a Preclinical Oral Chagas Disease Model. Preprints2024, 2024091328. https://doi.org/10.20944/preprints202409.1328.v1
APA Style
Pacini, M. F., Bulfoni Balbi, C., Dinatale, B., Farre, C., Cacik, P., Gonzalez, F. B., Marcipar, I., & Pérez, A. R. (2024). Intranasal Trans-Sialidase Vaccine Mitigates Acute and Chronic Pathology in a Preclinical Oral Chagas Disease Model. Preprints. https://doi.org/10.20944/preprints202409.1328.v1
Chicago/Turabian Style
Pacini, M. F., Ivan Marcipar and Ana Rosa Pérez. 2024 "Intranasal Trans-Sialidase Vaccine Mitigates Acute and Chronic Pathology in a Preclinical Oral Chagas Disease Model" Preprints. https://doi.org/10.20944/preprints202409.1328.v1
Abstract
Chagas disease, caused by Trypanosoma cruzi, leads to severe complications in 30% of infected individuals, including acute myocarditis and chronic fibrosing cardiomyopathy. Despite the significant burden of the disease, there is currently no licensed vaccine available to prevent it. This study aimed to evaluate the mucosal and systemic immunogenicity as well as the prophylactic efficacy of a mucosal vaccine and its impact on both acute and chronic cardiomyopathy. The results showed that nasal administration of Trans-sialidase (TS) plus c-di-AMP (TS+A). TS+A vaccine elicited NALT expression of IFN-γ, IL-17a, and IL-4 mRNA, and nasal-specific IgA production. Ex vivo challenge with TS also triggered enhanced proliferation of lymphocyte from the NALT, sentinel cervical lymph node and spleen. TS+A immunization increased plasma levels of Th1/Th2/Th17 cytokines and an evident cellular response to judge enhanced delayed-type hypersensitivity responses following TS footpad challenge. After oral infection, TS+A-vaccinated mice showed significantly reduced parasitemia and parasite load in heart, muscle and intestine, while markers of hepatic and muscle damage as well as clinical manifestations of acute infection are strongly diminished. TS+A also attenuated acute myocarditis and heart expression of inflammatory markers. The protection conferred by TS+A extended into the chronic phase, where it resulted in a clear reduction in chronic myocarditis, fibrosis, and functional electrocardiographic abnormalities, associated with decreased expression of the pro-fibrotic TGF-β. These results revealed that it is possible to develop a mucosal vaccine against T. cruzi based on TS and c-di-AMP, capable to reduce the development of Chagas cardiomyopathy, the hallmark of Chagas disease.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
