From Genome Screening to Creation of Vaccine Against Trypanosoma cruzi by Use of Immunoinformatics

Christian Teh-Poot, Evelyn Tzec-Arjona, Pedro Martinez-Vega, Maria Jesus Ramirez-Sierra, Miguel Rosado-Vallado, and Eric Dumonteil Laboratorio de Parasitologia, Centro de Investigaciones Regionales Dr Hideyo Noguchi, Universidad Autonoma de Yucatan, Merida, Mexico; and Department of Tropical Medicine, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and activation of CD8 T cells is crucial for a protective immune response. Therefore, the identification of antigens with major histocompatibility complex class I epitopes is a crucial step for vaccine development against T. cruzi. Our aim was to identify novel antigens and epitopes by immunoinformatics analysis of the parasite proteome (12 969 proteins) and to validate their immunotherapeutic potential in infected mice. We identified 172 predicted epitopes, using NetMHC and RANKPEP. The corresponding protein sequences were reanalyzed to generate a consensus prediction, and 26 epitopes were selected for in vivo validation. The interferon γ (IFN-γ) recall response of splenocytes from T. cruzi–infected mice confirmed that 10 of 26 epitopes (38%) induced IFN-γ production. The immunotherapeutic potential of a mixture of all 10 peptides was evaluated in infected mice. The therapeutic vaccine was able to control T. cruzi infection, as evidenced by reduced parasitemia, cardiac tissue inflammation, and parasite burden and increased survival. These findings illustrate the benefits of this approach for the rapid development of a vaccine against pathogens with large genomes. The identified peptides and the proteins from which they are derived are excellent candidates for the development of a vaccine against T. cruzi.