Your new experience awaits. Try the new design now and help us make it even better

ORIGINAL RESEARCH article

Front. Immunol.

Sec. Vaccines and Molecular Therapeutics

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1662036

This article is part of the Research TopicAdvancements in Vaccine Strategies for Chronic Infectious Disease ManagementView all articles

Nasal Vaccination Against Trypanosoma cruzi: A Dual Approach for Prevention and Treatment of Chronic Chagas Cardiomyopathy

Provisionally accepted
  • 1Universidad Nacional del Litoral, Santa Fe, Argentina
  • 2CONICET Santa Fe, Santa Fe, Argentina
  • 3CONICET Rosario, Rosario, Argentina
  • 4Universidad Nacional del Nordeste, Corrientes, Argentina

The final, formatted version of the article will be published soon.

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), is a neglected life-threatening disease. Given that available pharmacologic treatments are effective only in the acute phase, and that diagnosis typically occurs during the chronic phase when cardiac damage is already present, current efforts should aim to mitigate cardiac pathology during chronic infection. This study evaluates the effectiveness of a nasal vaccine based on trans-sialidase (TS) plus c-di-AMP in both prophylactic and therapeutic settings against chronic Chagas cardiomyopathy (CCC) in a mouse model of T. cruzi oral infection. Prophylactic and therapeutic vaccination significantly reduced cardiac inflammation, fibrosis, and parasite load. Histological analysis confirmed less cardiac damage in vaccinated groups compared to infected, unvaccinated controls. While electrocardiographic abnormalities were fully prevented in the prophylactic group, therapeutic vaccination still halved arrhythmia incidence, indicating functional benefits despite late administration. Immunologically, both vaccine regimens promoted a Th17-skewed response, with increased IL-17 expression in cardiac tissue. However, distinct immune signatures were observed: prophylactic vaccination reduced TGF-β and T-bet expression, correlating with less fibrosis and inflammation; therapeutic vaccination elevated Foxp3, suggesting regulatory T cell involvement in controlling chronic inflammation. Both strategies enhanced TS-specific antibodies and reduced non-protective, parasite-wide antibody responses, shifting the humoral profile toward functional protection. Importantly, vaccinated animals also showed a marked reduction in heart auto-reactive antibodies. The findings suggest that early intervention yields greater benefits, but even post-infection, immunization can also significantly mitigate cardiac damage. These results underscore the potential of nasal TS-based vaccines as a non-invasive, dual-action strategy to both prevent and treat CCC.

Keywords: Vaccine, Trypanosoma cruzi, Chronic infection, therapeutic, prophilactic

Received: 08 Jul 2025; Accepted: 29 Sep 2025.

Copyright: © 2025 Cacik, Pacini, Bulfoni Balbi, Dinatale, Diaz, Cha, Farre, Gianeselli, Prochetto, Pérez and Marcipar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Iván Sergio Marcipar, imarcipr@gmail.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.