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Drug-cured experimental Trypanosoma cruzi infections confer long-lasting and cross-strain protection
- Source :
- PLoS Neglected Tropical Diseases, PLoS Neglected Tropical Diseases, Vol 14, Iss 4, p e0007717 (2020)
- Publication Year :
- 2020
- Publisher :
- Public Library of Science (PLoS), 2020.
-
Abstract
- Background The long term and complex nature of Chagas disease in humans has restricted studies on vaccine feasibility. Animal models also have limitations due to technical difficulties in monitoring the extremely low parasite burden that is characteristic of chronic stage infections. Advances in imaging technology offer alternative approaches that circumvent these problems. Here, we describe the use of highly sensitive whole body in vivo imaging to assess the efficacy of recombinant viral vector vaccines and benznidazole-cured infections to protect mice from challenge with Trypanosoma cruzi. Methodology/Principal findings Mice were infected with T. cruzi strains modified to express a red-shifted luciferase reporter. Using bioluminescence imaging, we assessed the degree of immunity to re-infection conferred after benznidazole-cure. Those infected for 14 days or more, prior to the onset of benznidazole treatment, were highly protected from challenge with both homologous and heterologous strains. There was a >99% reduction in parasite burden, with parasites frequently undetectable after homologous challenge. This level of protection was considerably greater than that achieved with recombinant vaccines. It was also independent of the route of infection or size of the challenge inoculum, and was long-lasting, with no significant diminution in immunity after almost a year. When the primary infection was benznidazole-treated after 4 days (before completion of the first cycle of intracellular infection), the degree of protection was much reduced, an outcome associated with a minimal T. cruzi-specific IFN-γ+ T cell response. Conclusions/Significance Our findings suggest that a protective Chagas disease vaccine must have the ability to eliminate parasites before they reach organs/tissues, such as the GI tract, where once established, they become largely refractory to the induced immune response.<br />Author summary Chagas disease, which is caused by the protozoan parasite Trypanosoma cruzi, is a major public health problem throughout Latin America. Attempts to develop a vaccine have been hampered by technical difficulties in monitoring the extremely low parasite burden during the life-long chronic stage of infection. To circumvent these issues, we used highly sensitive bioluminescence imaging to assess the ability of recombinant viral vector vaccines and drug-cured infections to confer protection against experimental challenge in mice. We observed that drug-cured infections were much more effective than subunit vaccines. Efficacy was independent of the route of infection or size of the challenge inoculum, and was undiminished after almost a year. In addition, drug-cured infections conferred a high level of cross-strain protection. The highly sensitive imaging procedures enabled us to visualise parasite distribution in mice where full protection was not achieved. This suggested that to confer protection, vaccines must prevent the infection of organs/tissues that act as parasite reservoirs during the chronic stage. Once established at these sites, parasites become largely refractory to vaccine-induced elimination.
- Subjects :
- Protozoan Vaccines
0301 basic medicine
Life Cycles
Luminescence
RC955-962
Protozoology
White Blood Cells
0302 clinical medicine
Animal Cells
Arctic medicine. Tropical medicine
Medicine and Health Sciences
Immune Response
Protozoans
Mice, Inbred BALB C
Vaccines, Synthetic
Vaccines
biology
T Cells
Physics
Electromagnetic Radiation
Vaccination
Eukaryota
In Vivo Imaging
Infectious Diseases
Benznidazole
Vaccines, Subunit
Physical Sciences
Female
Protozoan Life Cycles
Public aspects of medicine
RA1-1270
Bioluminescence
Cellular Types
Research Article
medicine.drug
Chagas disease
Trypanosoma
Infectious Disease Control
Imaging Techniques
Trypanosoma cruzi
Immune Cells
Immunology
030231 tropical medicine
Heterologous
Immunity, Heterologous
Research and Analysis Methods
Microbiology
Viral vector
03 medical and health sciences
Immune system
Immunity
Parasitic Diseases
medicine
Animals
Bioluminescence imaging
Chagas Disease
Blood Cells
business.industry
Organisms
Public Health, Environmental and Occupational Health
Biology and Life Sciences
Cell Biology
Trypomastigotes
medicine.disease
biology.organism_classification
Parasitic Protozoans
Disease Models, Animal
030104 developmental biology
business
Developmental Biology
Subjects
Details
- ISSN :
- 19352735 and 19352727
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- PLOS Neglected Tropical Diseases
- Accession number :
- edsair.doi.dedup.....f6c8b1bc864701d71e6e781dc6e19c8f