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The Trypanosoma cruzi TcTASV-C protein subfamily administrated with U-Omp19 promotes a protective response against a
Lucas D Caeiro1, Yamil E Masip1, Mariana Rizzi1
1Instituto de Investigaciones Biotecnológicas (IIBio), Universidad Nacional de San Martín (UNSAM) - CONICET, Av. 25 de Mayo y Francia, Campus UNSAM, San Martín (1650), Provincia de Buenos Aires, Argentina.
Abstract:
The development of a Chagaś disease vaccine has yet the need for the identification of novel combinations of antigens and adjuvants. Here, the performance of TcTASV-C proteins that are virulence factors of trypomastigotes and belong to a novel surface protein family specific for T. cruzi, have been evaluated as antigens for a prophylactic vaccine. Several immunization schemes in which TcTASV-C was combined with aluminum hydroxide, saponin and/or U-Omp19 were assayed. Aluminum hydroxide and saponin were assayed together to trigger different pathways of the immune response simultaneously. U-Omp19 is a promising novel adjuvant able to promote a Th1 immune response with IFNg production, thus an interesting molecule to be tested as adjuvant for the control of T. cruzi infection. Therefore, U-Omp19 was added to the aluminum hydroxide-saponin formulation as well as assayed individually with TcTASV-C. The immunization with TcTASV-C and U-Omp19 had the best performance as a prophylactic vaccine. Mice presented the lowest parasitemias and improved survival by 40% after being challenged with a highly virulent T. cruzi strain, which promoted 100% mortality in all other immunized groups. Immunization with TcTASV-C and U-Omp19 triggered cellular responses with IFN-γ and IL-17 production and with lytic antibodies that could explain the protection achieved by this vaccination scheme. To our knowledge, this is the first time that U-Omp19 is tested with a defined T. cruzi antigen in a vaccine formulation.
Insights
Developing a Chagas disease vaccine requires new antigen and adjuvant combinations. TcTASV-C protein with U-Omp19 adjuvant showed the best performance, significantly improving mouse survival against Trypanosoma cruzi infection.
Area of Science:
- Immunology
- Vaccinology
- Parasitology
Background:
- Chagas disease vaccine development necessitates novel antigen and adjuvant strategies.
- TcTASV-C proteins, T. cruzi virulence factors, represent a new class of specific surface antigens.
- Adjuvants like U-Omp19 are crucial for eliciting effective immune responses against T. cruzi.
Purpose of the Study:
- Evaluate TcTASV-C proteins as antigens in a prophylactic Chagas disease vaccine.
- Assess various immunization schemes combining TcTASV-C with aluminum hydroxide, saponin, and/or U-Omp19.
- Identify the optimal antigen-adjuvant combination for inducing protective immunity against T. cruzi.
Main Methods:
- Assayed immunization schemes using TcTASV-C with aluminum hydroxide, saponin, and U-Omp19.
- Tested U-Omp19 individually and in combination with aluminum hydroxide and saponin.
- Challenged immunized mice with a virulent T. cruzi strain to evaluate vaccine efficacy.
Main Results:
- Immunization with TcTASV-C and U-Omp19 demonstrated the best prophylactic vaccine performance.
- This group exhibited the lowest parasitemia and 40% improved survival compared to controls.
- The TcTASV-C and U-Omp19 combination induced cellular responses (IFN-γ, IL-17) and lytic antibodies.
Conclusions:
- TcTASV-C combined with U-Omp19 is a promising candidate for a Chagas disease vaccine.
- This formulation effectively controls parasitemia and enhances survival in a T. cruzi challenge model.
- This study represents the first evaluation of U-Omp19 with a defined T. cruzi antigen in a vaccine.
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