Recombinant Mycobacterium bovis BCG is a promising platform to develop vaccines against Trypansoma cruzi infection

Author:

Bontempi I12,Leal K3,Prochetto E1,Díaz G1,Cabrera G12,Bortolotti A4,Morbidoni H R4,Borsuk S3,Dellagostin O3,Marcipar I12ORCID

Affiliation:

1. Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Santa Fe, Argentina

2. Facultad de Ciencias Médicas, Universidad Nacional del Litoral, Santa Fe, Argentina

3. Núcleo de Biotecnologia, CDTec, Universidade Federal de Pelotas, Pelotas, Brazil

4. Laboratorio de Microbiología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina

Abstract

Summary Chagas disease, caused by the hemoflagelate parasite Trypanosoma cruzi, is one of the most prevalent endemic parasitoses, affecting 7–8 million people. Due to the complexity of the infection, no vaccines are availabel at present. The extraordinary adjuvant capacity of bacille Calmette–Guérin (BCG) was explored in this work to develop a vaccine candidate to protect against T. cruzi infection using the recombinant BCG (rBCG) vaccine platform. Three antigens of the parasite corresponding to the N and C terminal fragments of the enzyme trans-sialidase (NT-TS and CT-TS, respectively) and a fragment of the cruzipain enzyme (CZf) were cloned into the vectors pUS997 and pUS2000 and transformed into the BCG Pasteur strain. In vaccinated mice, rBCG expressing NT-TS in pUS2000 plasmid provided the highest protection and the lowest parasitemia after challenging BALB/c mice with a 50% lethal dose of parasites. When mice vaccinated with pUS2000-NT-TS were challenged with a 100% lethal dose of parasite, high levels of protection were also obtained, together with a low degree of cardiac lesions 120 days after infection. In immunized mice with pUS2000-NT-TS/rBCG clone, the proliferation of CD4+ cells from splenocytes stimulated with the TS antigen was significant; this stimulation increased interferon (IFN)-γ and interleukin (IL)-17 within CD4⁺ T lymphocytes (LTCD4+) cells and IFN-γ and CD107 expression within LTCD8+ cells. Therefore, pUS2000-NT-TS/rBCG conferred high levels of protection, which correlated with an immune response orientated towards a T helper type 1 (Th1)/Th17 profile, together with an LTC-specific response, indicating that rBCG is a promising platform to develop vaccines against T. cruzi.

Funder

Fondo para la Investigación Científica y Tecnológica

Consejo Nacional de Investigaciones Científicas y Técnicas

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

Reference38 articles.

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