Synthetic glycovaccines elicit cross-protection against Chagas disease and tegumentary leishmaniasis in a murine co-infection model

Abstract

Abstract Chagas disease (CD) and tegumentary leishmaniasis (TL) are two of the World Health Organization’s (WHO) top 20 neglected tropical diseases. These diseases are caused by the protozoan trypanosomatids, Trypanosoma cruzi and Leishmania spp., respectively. Although historically restricted to Central and South American, there are currently, ~7 million people infected with CD worldwide, with ~300,000 chronically infected patients in the US. Between 700,000 and 1.2 million new cases of TL occur worldwide yearly. Chemotherapeutic agents are available for the treatment of both diseases; however, they may cause serious adverse events, ultimately resulting in premature treatment interruption. Moreover, no effective vaccine for either disease is currently available. Due to the evolutionary loss of the α1,3-galactosyltransferase (α1,3GT) gene in humans and Old-World nonhuman primates, α-Gal epitopes, abundantly expressed on both Trypanosoma cruzi and Leishmania spp. cell surfaces, are highly immunogenic. We, therefore, hypothesize that a synthetic glycan-based vaccine could provide effective cross-protection against a T. cruzi and L. major co-infection. Here we use an α1,3GT-knockout (α1,3GT-KO) murine model to evaluate the efficacy of two new synthetic neoglycoproteins, NGP28b and NGP29b, containing nonreducing, terminal α-Gal and β-Galf glycotopes, respectively, as potential vaccine candidates against CD and TL. Our data indicate that both vaccine candidates induce a strong cross-protective immune response, significantly reducing parasite burden and increasing animal survival in this co-infection experimental model This study was partially supported by a grant NIH-U54MD007592 (to Robert A. Kirken (PI), ICA (Co-I)), from the National Institute on Minority Health and Health Disparities (NIMHD). We would like to thank the staff of the Border Biomedical Research Center (BBRC) Biomolecule Analysis Omics Unit (BAOU). BAOU was supported by the NIMHD grant 5U54MD007592. CDK was supported by the UT System LSAMP program which is funded by the National Science Foundation grant number HRD-1202008.