A synthetic peptide from Trypanosoma cruzi mucin-like associated surface protein as candidate for a vaccine against Chagas disease

Abstract

Chagas disease, caused by Trypanosoma cruzi, is responsible for producing significant morbidity and mortality throughout Latin America. The disease has recently become a public health concern to nonendemic regions like the U.S. and Europe. Currently there are no fully effective drugs or vaccine available to treat the disease. The mucin-associated surface proteins (MASPs) are glycosylphosphatidylinositol (GPI)-anchored glycoproteins encoded by a multigene family with hundreds of members. MASPs are among the most abundant antigens found on the surface of the infective trypomastigote stage of T. cruzi, thus representing an attractive target for vaccine development. Here we used immunoinformatics to select a 20-mer peptide with several predicted overlapping B-cell, MHC-I, and MHC-II epitopes, from a MASP family member expressed on mammal-dwelling stages of T. cruzi. The synthetic MASP peptide conjugated to keyhole limpet hemocyanin (MASPpep-KLH) was tested in presence or not of an adjuvant (alum, Al) as a vaccine candidate in the C3H/HeNsd murine model of T. cruzi infection. In considerable contrast to the control groups receiving placebo, Al, or KLH alone or the group immunized with MASPpep-KLH/Al, the group immunized with MASPpep-KLH showed 86% survival rate after challenge with a highly lethal dose of trypomastigotes. As evaluated by quantitative real-time polymerase chain reaction, MASPpep-KLH-immunized animals had much lower parasite load in the heart, liver, and spleen than control animals. Moreover, protected animals produced trypanolytic, protective antibodies, and a cytokine profile conducive to resistance against parasite infection. Finally, in vivo depletion of either CD4+ or CD8+T cells indicated that the latter are critical for protection in mice immunized with MASPpep-KLH. In summary, this new peptide-based vaccine with overlapping B- and T-cell epitopes is able to control T. cruzi infection in mice by priming both humoral and cellular immunity.

Extracellular Vesicles: Role in Inflammatory Responses and Potential Uses in Vaccination in Cancer and Infectious Diseases

“…Mucins containing α -gal residues elicit high titers of IgG antibodies decreasing parasitemia during the chronic phase [ 131 ]. Therefore, the production and release of EVs might have a key role in the establishment of infection and may be considered a platform to develop preventive or prophylactic vaccines for Chagas disease [ 132 ].…”

Cysteine mutagenesis improves the production without abrogating antigenicity of a recombinant protein vaccine candidate for human chagas disease

“…19 Specifically, vaccination of mice with a synthetic peptide containing predicted overlapping antigenic epitopes from T. cruzi mucin-like associated surface protein increased survival in mice with a reduction in parasite load in the heart. 20 Immunization of adenovirus carrying amastigote surface protein-2 and trans-sialidase antigens, 21 and plasmids expressing TcG1, TcG2, or TcG4, membrane associated glycosylphosphatidylinositol (GPI) proteins expressed on the surface of T. cruzi 22 resulted in reduced parasite burden in tissue, reduced heart injury and increased survival. Our laboratory has been developing a therapeutic Chagas vaccine based on the Tc24 protein, a T. cruzi parasite excretory-secretory protein, by itself or combined with additional antigens and in the presence of one or more adjuvants.…”

High-resolution profiling of linear B-cell epitopes from mucin-associated surface proteins (MASPs) of Trypanosoma cruzi during human infections

“…More recently, Serna et al . showed that a peptide bearing a quite complex array of MHC I, MHC II and B-cell epitopes, and restricted to a single MASP molecule (TcCLB.511603.380) was recognized by a panel of chronic Chagasic patients [ 57 ]. Unfortunately, these results were published a posteriori of the Chagas-chip design, and hence this sequence was not included in our assays.…”