A synthetic peptide fromTrypanosoma cruzimucin-like associated surface protein as candidate for a vaccine against Chagas disease

• Published in: Vaccine Vol. 32; no. 28; p. 3525
• Main Authors: Serna, Carylinda, Lara, Joshua A, Rodrigues, Silas P, Marques, Alexandre F, Almeida, Igor C, Maldonado, Rosa A
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 12.06.2014
• Subjects: Cytokines; Deoxyribonucleic acid; DNA; Glycoproteins; Immunization; Infections; Lymphocytes; Mammals; Mortality; Parasites; Peptides; Protected animals; Protozoa; Public health; Survival; Vaccines; Vector-borne diseases
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2014.04.026

Chagas disease, caused byTrypanosoma 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 ofT. 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 ofT. 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 ofT. cruziinfection. 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 controlT. cruziinfection in mice by priming both humoral and cellular immunity.