• Vaccine Name: T. cruzi DNA vaccine encoding PFR2 fused with HSP70
• Target Pathogen: Trypanosoma cruzi
• Target Disease: Chagas disease
• Product Name: pCMV4-PFR2-H70
• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: Mouse
• Antigen: PFR2 and PFR3 genes (Morell et al., 2006) - paraflagellar rod proteins present in the flagellum of T. cruzi that induce an immune respons that results in reduction in the level of circulating parasites.
• Tc00.1047053434931.10 gene engineering:
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click Here.
• Immunization Route: Intramuscular injection (i.m.)
• Description: T. cruzi DNA vector vaccine containing the PFR2 and PFR3 genes fused to HSP70

Mouse Response

• Host Strain: BALB/c + C57BL/6
• Vaccination Protocol: Groups of nine BALB/c and of five C57BL/6-A2.1/Kb mice were intramuscularly injected with 100 μg of plasmids: pCMV4 (control), pCMV4-PFR2, and pCMV4-PFR3 (carrying PFR2 and PFR3 gene, respectively) and pCMV4-PFR2-H70 and pCMV4-PFR3-H70 (bearing the PFR2-HSP70 and PFR3-HSP70 fused genes, respectively) in 100 μl. Sterile 0.9% sodium chloride solution was injected to the control group. Each mouse was immunized four times at 3-week intervals. Groups of five immunized BALB/c and B6-A2/Kb mice were used to determine the induced cellular response. (Morell et al., 2006)
• Immune Response: High antibody titers were present 2 weeks after the third dose in the sera of the BALB/c mice immunized with the constructs containing the PFR2 gene alone or fused to HSP70 gene. The mice immunized with the plasmid bearing only the PFR3 gene or fused to the HSP70 gene also reached significant anti-PFR3 reactivity after the fourth immunization. The percentage of spleen cells expressing IFN-γ and IL12 was significantly higher (p < 0.05) in mice immunized with the PFR2-HSP70 fused genes than that observed in mice that received saline solution, empty pCMV4 vector or the PFR2 coding gene alone. In the mice immunized with the PFR2-HSP70 fused genes a lower percentage of cells expressing IL4 was also observed relative to that observed in mice that received saline solution, empty pCMV4 vector or the PFR2 coding gene alone. In contrast, an increase in the number of cells expressing IL-4 was observed in mice immunized with the PFR3-HSP70 fused genes, although it was not statistically significant. (Morell et al., 2006)
• Challenge Protocol: Groups of four immunized BALB/c mice were challenged with 2.5 × 103 of attenuated trypomastigote forms 10 weeks after the last immunization. The protection assays were carried in two of the three experiments done to analyze the immune response. (Morell et al., 2006)
• Efficacy: Two out of eight control mice that received saline solution died at days 26 and 27 post-infection. One mouse of the group of eight mice inoculated with pCMV4 died at day 30 post-infection. In contrast, in mice immunized with the PFR2 gene or the PFR2-HSP70 construct circulating parasites could be detected only the first 3 weeks post-infection. Parasites could not be detected afterwards. Mice immunized with the PFR3 gene or the PFR3-HSP70 construct were able to control infection at week fourth post-infection. Controls mice controlled infection at week fifth post-infection. (Morell et al., 2006)