DNA and Protein Composite Vaccine Produces Long Lasting Immunity Against Chagas Disease in Mice

A candidate vaccine for Chagas disease was found to induce long-lasting immunity against the Trypanosoma cruzi parasite in mice.

Chagas disease, or American trypanosomiasis, is a tropical parasitic disease caused by the protozoan Trypanosoma cruzi. It is spread mostly by insects known as Triatominae or kissing bugs. The symptoms change over the course of the infection. In the early stage, symptoms are typically either not present or mild and may include fever, swollen lymph nodes, headaches, or local swelling at the site of the bite. After eight to 12 weeks, individuals enter the chronic phase of disease, and in 60%–70% of cases it never produces further manifestations. The other 30%–40% of people develop further symptoms 10 to 30 years after the initial infection, including enlargement of the ventricles of the heart in 20%–30% of cases, which may lead to heart failure.

Investigators at the University of Texas Medical Branch (Galveston, USA) had previously obtained promising results with a vaccine that contained three particular parasite proteins. In the current study, they expanded on the earlier work by vaccinating mice with a combination of two of the T. cruzi proteins (TcG2 and TcG4), which had proven to be the most potent in provoking both an antibody and a T-cell immune response.

The investigators immunized C57BL/6 mice with the TcG2/TcG4 vaccine delivered by a DNA-prime/Protein-boost (D/P) approach. In this procedure the first injection contained DNA coding for the TcG2 and TcG4 proteins, and the second, three weeks later, contained a mix of the two proteins themselves. Some mice were also given a booster immunization three months later, which consisted of the mix of the two proteins (D/P/P regimen).

Results published in the May 7, 2015, online edition of the journal PLOS Pathogens revealed that mice challenged with T. cruzi immediately after immunization with the D/P vaccine were capable of controlling 90%–97% of the acute parasitemia and tissue parasite burden, and, subsequently, inflammatory infiltrate and tissue fibrosis were particularly absent in the heart and skeletal muscle of vaccinated mice.

D/P vaccination elicited CD4+ (30-38%) and CD8+ (22-42%) T-cells that maintained an effector phenotype up to 180 days following vaccination and were capable of responding to antigenic stimulus or challenge infection by a rapid expansion with type I cytokine production and cytolytic T-lymphocyte activity. Subsequently, challenge infection at 120 or 180 days following vaccination, resulted in two to three-fold lower parasite burden in vaccinated mice than was noted in unvaccinated/infected mice.

Summing up the results, the investigators said, "The TcG2/TcG4 D/P vaccine provided long-term anti-T. cruzi T-cell immunity, and booster immunization would be an effective strategy to maintain or enhance the vaccine-induced protective immunity against T. cruzi infection and Chagas disease. The next steps toward clinical studies in humans will include characterizing the quality and quantity of immunity to the vaccine candidates in naïve individuals."

Related Links:
University of Texas Medical Branch