α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model

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.

Leishmaniasis and Chagas disease: Is there hope in nanotechnology to fight neglected tropical diseases?

“…Several T. cruzi proteins are able to promote cardiac damage in the absence of live parasites by inducing autoimmunity in animal models (Cunha-Neto et al, 1996;Bonney et al, 2011). Fortunately, a number of other recombinant T. cruzi proteins as well as attenuated T. cruzi parasites are emerging as potentially safe strategies for the development of a CD vaccine (Sańchez-Valdeź et al, 2015;Rios et al, 2019;da Costa et al, 2021;Rodrigues da Cunha et al, 2021). Researchers are also testing mRNA vaccines after their successful use in COVID-19 (Diaz-Hernandez et al, 2022;Maldonado et al, 2022).…”

The α-Galactosyl Carbohydrate Epitope in Pathogenic Protozoa

“…Vaccination of knockout mice with synthetic α-gal-based vaccines (α-(1 → 3)-GalT knockout mice) was beneficial in both the acute and chronic stage of the disease. Cytokine production was improved, and the parasitemia was controlled in the first stage of the infection, showing a lowering of heart inflammation and clearance of amastigote parasites from the heart tissue in the acute and chronic stages. , …”

“…Also, neoglycoconjugates containing the α-gal glycotope have been evaluated as diagnostic tools for Chagas disease. ,− The syntheses of these antigens will be discussed below.…”

“…Cytokine production was improved, and the parasitemia was controlled in the first stage of the infection, showing a lowering of heart inflammation and clearance of amastigote parasites from the heart tissue in the acute and chronic stages. 72,76 Glycans in Trypanosoma brucei. T. brucei is the agent of the African trypanosomiasis known as sleeping sickness, transmitted by the tsetse fly, whose diagnosis and treatment are complex.…”

A Ferrier glycosylation/cis-dihydroxylation strategy to synthesizeLeishmaniaspp. lipophosphoglycan-associated βGal(1,4)Man disaccharide

“…Because of our interest in anti-parasitic immunotherapies 12 and the development of virus-like particles (VLP) glycoconjugates to boost anti-carbohydrate immune responses, 13 we have centered our attention on LPG to explore VLP-conjugated anti-leishmaniasis vaccine candidates. Here, we report an expeditious synthetic route to prepare Galβ(1→4)Man, a disaccharide exclusively found in the linear phosphoglycan and the capping oligosaccharides of Leishmania's LPG.…”