Recombinant Enolase of Trypanosoma cruzi as a Novel Vaccine Candidate against Chagas Disease in a Mouse Model of Acute Infection.

Minerva Arce-Fonseca,Verónica Graullera-Rivera,José Luis Rosales-Encina,Alberto Aranda-Fraustro,Olivia Rodríguez-Morales,María Cristina González-Vázquez,Pedro A Reyes,Alejandro Carabarin-Lima

doi:10.1155/2018/8964085

Abstract

Trypanosoma cruzi is the protozoan parasite that causes Chagas disease, which is considered by the World Health Organization to be a neglected tropical disease. Two drugs exist for the treatment of Chagas disease, nifurtimox and benznidazole; they are only effective in the acute phase, and a vaccine is currently not available. In this study, we used the recombinant enolase from T. cruzi H8 strain (MHOM/MX/1992/H8 Yucatán) (rTcENO) and its encoding DNA (pBKTcENO) to immunize mice and evaluate their protective effects in an experimental murine model of acute phase infection. Our results showed that mice vaccinated with rTcENO or its encoding DNA were able to generate typical specific antibodies (IgG1, IgG2a, and IgG2b), suggesting that a mixed Th1/Th2 immune response was induced. The parasite burden in the blood was reduced to 69.8% and 71% in mice vaccinated with rTcENO and pBKTcENO, respectively. The group vaccinated with rTcENO achieved 75% survival, in contrast to the group vaccinated with pBKTcENO that showed no survival in comparison to the control groups. Moreover, rTcENO immunization elevated the production of IFN-γ and IL-2 after the parasite challenge, suggesting that the Th1-type immune response was polarized. These results indicated that rTcENO could be used as a vaccine against Chagas disease.

Highlights

The intracellular protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, considered as a neglected tropical disease [1]
We found that immunization with rTcENO, but not with pBKTcENO, induced substantial protection in mice, indicating that rTcENO could be a good candidate to develop a vaccine against Chagas disease
The endotoxin level of rTcENO used for immunization was found to be

Summary

Introduction

The intracellular protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, considered as a neglected tropical disease [1]. Because of its natural life cycle, involving mitotic division in reduviid insects, which transmit the infection by feeding on the blood of different vertebrates, T. cruzi is considered to be a severe health problem in rural areas of Mexico and Central and South America, where these insects are endemic. In Mexico, as well as in other endemic countries, cases are becoming more common in urban areas. This shift in the epidemiology of Chagas disease is connected to the migration of people infected with T. cruzi, blood transfusion, vertical transmission (mother to child), and organ transplantation [9]

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Results

Conclusion