Abstract
Chagas disease, caused by the parasite Trypanosoma cruzi, is considered endemic in more than 20 countries but lacks both an approved vaccine and limited treatment for its chronic stage. Chronic infection is most harmful to human health because of long-term parasitic infection of the heart. Here we show that immunization with a virus-like particle vaccine displaying a high density of the immunogenic α-Gal trisaccharide (Qβ-αGal) induced several beneficial effects concerning acute and chronic T. cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ and IL-12 cytokine production, and controlled parasitemia in the acute phase at 8 days post-infection (dpi) for the Y strain and 22 dpi for the Colombian strain. In the chronic stage of infection (36 and 190 dpi, respectively), all of the vaccinated group survived, showing significantly decreased heart inflammation and clearance of amastigote nests from the heart tissue.
Highlights
We describe a vaccine candidate based on a carbohydrate found on the T. cruzi cell surface, linked in the vaccine to a virus-like particle that provides a strong and focused immune response
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, commonly transmitted through the feces of the infected reduviid bug
It is estimated that 7 million people are infected with T. cruzi, with approximately 18,000 new cases each year, [2] representing a serious health problem in Latin America that is spreading in the U.S [3] and globally [4]
Summary
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, commonly transmitted through the feces of the infected reduviid bug (kissing bug). Treatment is limited to the two drugs available, nifurtimox and benznidazole. Their efficacy in the acute phase of the disease is questionable, [9] costly, and significant side effects can present as gastrointestinal distress; cutaneous hypersensitivity and neurological symptoms have been reported.[10] With no vaccine currently available for Chagas disease, [11,12] a new immunological approach is needed [13,11,14]. An extensive range of vaccine formulations has been assessed in recent years, from the use of whole attenuated parasites to purified or recombinant proteins, viral vectors, and DNA vaccines [15,16,17,18,19]
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