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Safety and immunogenicity of a recombinant vaccine against Trypanosoma cruzi in Rhesus macaques
- Source :
- Vaccine
- Publication Year :
- 2020
-
Abstract
- Chagas disease, caused by the protozoan parasite Trypanosoma cruzi is one of the most important neglected parasitic diseases in the Americas. Vaccines represent an attractive complementary or even an alternative for the control of T. cruzi infection and pre-clinical studies in mice demonstrated that trypomastigote surface antigen (TSA-1) and the flagellar calcium-binding (Tc24) parasite antigens are promising candidates for vaccine development. We performed here the first evaluation of the safety and immunogenicity of two recombinant vaccine antigens (named TSA1-C4 and Tc24-C4) in naïve non-human primates. Three rhesus macaques received 3 doses of each recombinant protein, formulated with E6020 (Eisai Co., Ltd.), a novel Toll-like receptor-4 agonist, in a stable emulsion. All parameters from blood chemistry and blood cell counts were stable over the course of the study and unaffected by the vaccine. A specific IgG response against both antigens was detectable after the first vaccine dose, and increased with the second dose. After three vaccine doses, stimulation of PBMCs with a peptide pool derived from TSA1-C4 resulted in the induction of TSA1-C4-specific TNFα-, IL-2-and IFNγ-producing CD4(+) in one or two animals while stimulation with a peptide pool derived from Tc24-C4 only activated IFNγ-producing CD4(+)T cells in one animal. In two animals there was also activation of TSA1-C4-specific IL2-producing CD8(+) T cells. This is the first report of the immunogenicity of T. cruzi-derived recombinant antigens formulated as an emulsion with a TLR4 agonist in a non-human primate model. Our results strongly support the need for further evaluation of the preventive efficacy of this type of vaccine in non-human primates and explore the effect of the vaccine in a therapeutic model of naturally-infected Chagasic non-human primates, which would strengthen the rationale for the clinical development as a human vaccine against Chagas disease.
- Subjects :
- Chagas disease
Protozoan Vaccines
Trypanosoma cruzi
030231 tropical medicine
Antigens, Protozoan
CD8-Positive T-Lymphocytes
Peripheral blood mononuclear cell
Article
law.invention
03 medical and health sciences
Mice
0302 clinical medicine
Antigen
law
medicine
Animals
Chagas Disease
030212 general & internal medicine
Vaccines, Synthetic
General Veterinary
General Immunology and Microbiology
biology
Immunogenicity
Public Health, Environmental and Occupational Health
biology.organism_classification
medicine.disease
Virology
Macaca mulatta
Infectious Diseases
Blood chemistry
Recombinant DNA
Molecular Medicine
CD8
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Vaccine
- Accession number :
- edsair.doi.dedup.....19e21716313af610f63c810cdc656965