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

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.

Cruzipain and Its Physiological Inhibitor, Chagasin, as a DNA-Based Therapeutic Vaccine Against Trypanosoma cruzi

“…Our results are in line with diverse approaches exhibiting the efficacy of several T. cruzi antigens (ASP-2, enolase, TSA-1, and Tc24) to control T. cruzi infection when they are tested as a therapeutic vaccine during the acute phase of the parasite infection ( 47 , 48 , 52 – 54 ). Nevertheless, only a few groups evaluated the performance of a therapeutic vaccine when it is administered during the chronic phase of T. cruzi infection ( 38 , 43 , 55 – 57 ).…”

Evaluation of pathogen P21 protein as a potential modulator of the protective immunity induced by Trypanosoma cruzi attenuated parasites

“…1 C). It has been shown that several T. cruzi recombinant proteins are able to generated Th1-driven antibodies in vaccinated mice; 21 , 22 , 23 however, elevated levels of anti-rP21 IgG1 were detected in rP21 primed animals indicating that a Th1 bias profile for a T. cruzi recombinant protein is not always the rule. The Th2 profile found in TCC+rP21 immunised animals, with a predominance of anti- T. cruzi IgG1 antibodies and a lower proportion of anti- T. cruzi IgG2c antibodies, was similar to the one obtained for TCC primed animals, indicating that the addition of rP21 did not alter this profile ( Fig.…”

Immunization with recombinant enolase ofSporothrixspp (rSsEno) confers effective protection against sporotrichosis in mice

“…Enolase has been described as a moonlighting protein that exhibits multiple nonglycolytic functions, probably because of its different multimeric structures 32 . Ehinger et al 39 reported that a-enolase of Streptococcus pneumonia forms an octamer in solution and that due to its binding to human plasminogen, it probably resides on the cellular surface of this pathogen and can be involved in virulence.…”

“…Enolase has been identified on the cell surface of C. albicans 24 , Plasmodium falciparum 25 , Ascaris suum 26 , Streptococcus sobrinus 27 , S. suis serotipo II 28 , S. iniae 29 , Plasmodium spp 30 and Clonorchis sinensis 31 . In addition, the immunogenicity and protective properties of anti-enolase immune response have been reported for diverse pathogens 24,27,32 .…”