Evaluation of the Immunoprotective Potential of Recombinant Paraflagellar Rod Proteins of Trypanosoma evansi in Mice

Abstract

Trypanosomosis, caused by Trypanosoma evansi, is an economically significant disease of livestock. Systematic antigenic variation by the parasite has undermined prospects for the development of a protective vaccine that targets the immunodominant surface antigens, encouraging exploration of alternatives. The paraflagellar rod (PFR), constituent proteins of the flagellum, are prominent non-variable vaccine candidates for T. evansi owing to their strategic location. Two major PFR constituent proteins, PFR1 (1770bp) and PFR2 (1800bp), were expressed using Escherichia coli. Swiss albino mice were immunized with the purified recombinant TePFR1 (89KDa) and TePFR2 (88KDa) proteins, as well as with the mix of the combined proteins at equimolar concentrations, and subsequently challenged with virulent T. evansi. The PFR-specific humoral response was assessed by ELISA. Cytometric bead-based assay was used to measure the cytokine response and flow cytometry for quantification of the cytokines. The recombinant TePFR proteins induced specific humoral responses in mice, including IgG1 followed by IgG2a and IgG2b. A balanced cytokine response induced by rTePFR 1 and 2 protein vaccination associated with extended survival and improved control of parasitemia following lethal challenge. The observation confirms the immunoprophylactic potential of the covert antigens of T. evansi.

The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples

“…Strategies included intracellular targets inaccessible to antibody attack (such as tubulin) and implemented most often extremely short waiting periods between boost and challenge, making it hard to grasp which immunological principle would have been triggered to provide protection. A recent study on the use of the T. evansi paraflagellar rod proteins PFR1 and PFR2, in which the infection challenge was performed only 7 days after the last vaccine boost, showed that the presence of high anti-target IgG titers at the moment of parasite challenge could delay the onset of parasitemia, but in the end failed to provide any sterile protection [ 103 ]. Most recently, it was shown that an anti- T. vivax vaccine using the ectodomain of the invariant cell-surface flagellum antigen IFX conferred protection against a subsequent T. vivax challenge in 10/15 mice, and that protection was observed even when parasite challenges were performed repeatedly over a 100-day period following the last vaccine boost.…”