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Vaccine Detail

T. cruzi vaccine encoding TcG2 and TcG4
Vaccine Information
  • Vaccine Name: T. cruzi vaccine encoding TcG2 and TcG4
  • Target Pathogen: Trypanosoma cruzi
  • Target Disease: Chagas disease
  • Type: DNA vaccine
  • Status: Research
  • Host Species for Licensed Use: Human
  • Antigen: TcG2 and TcG4 (Gupta et al., 2019) - antigens phylogenetically conserved in clinically important T. cruzi strains, expressed in infective and intracellular stages of the parasite, and recognized by parasite-specific cellular and humoral immune responses in multiple T. cruzi-infected hosts (Bhatia et al., 2004).
  • G2 gene engineering:
    • Type: DNA vaccine construction
    • Description:
    • Detailed Gene Information: Click Here.
  • protein G4 gene engineering:
    • Type: DNA vaccine construction
    • Description:
    • Detailed Gene Information: Click Here.
  • Adjuvant:
  • Immunization Route: Intramuscular injection (i.m.)
  • Description: A DNA vaccine containing recombinant proteins TcG2 and TcG4 formulated with fTr (fixed T. rangeli) epimastigotes (Gupta et al., 2019).
Host Response

Mouse Response

  • Host Strain: C57BL/6
  • Host age: 6 - week - old
  • Host gender: Female
  • Vaccination Protocol: Mice were vaccinated in following groups: DNA vaccine only, two doses; DNA vaccine + fTr, two doses; DNA vaccine + QA, two doses; DNA vaccine + fTr + QA, two doses. To determine if fTr boosts the DNA vaccine-induced immune responses, mice were vaccinated with DNA vaccine followed by fTr (gp5) or fTr+QA (gp6). Each dose of DNA vaccine was constituted of 25-μg of each plasmid (pCDNA3.TcG2 and pCDNA3.TcG4) and delivered in 100 μl PBS by intramuscular (im) injection in the hind thighs. When used, fTr (1 × 108 Tr in 100 μl PBS) was delivered by subcutaneous (sc) injection. When added, vaccine was emulsified with 5 μg QA per dose per mouse. Non-vaccinated (N) mice were used as controls. Prime and booster doses of vaccine were given at 21-day intervals. (Gupta et al., 2019)
  • Immune Response: TcG2/TcG4 vaccine adjuvanted with fTr also resulted in maximal levels of Tc-specific IgG sub-types. Tr-specific IgGs constituted of IgG1, IgG2a, and IgG2b subtypes were also detected in mice that received fTr as an adjuvant with TcG2/TcG4 DNA or as a booster vaccine, and maximal Tr-specific antibodies were measured in sera of mice given fTr as an adjuvant with TcG2/TcG4. (Gupta et al., 2019)
  • Challenge Protocol: Mice were immunized, challenged with Tc (10,000 trypomastigotes/mouse, intraperitoneal) at 21 days after the 2nd vaccine dose, and euthanized at 21 days' post-infection (pi). Non-vaccinated mice infected with Tc (T) and euthanized at similar time-points were used as controls. (Gupta et al., 2019)
References
Bhatia et al., 2004: Bhatia V, Sinha M, Luxon B, Garg N. Utility of the Trypanosoma cruzi sequence database for identification of potential vaccine candidates by in silico and in vitro screening. Infection and immunity. 2004; 72(11); 6245-6254. [PubMed: 15501750].
Gupta et al., 2019: Gupta S, Salgado-Jiménez B, Lokugamage N, Vázquez-Chagoyán JC, Garg NJ. TcG2/TcG4 DNA Vaccine Induces Th1 Immunity Against Acute Trypanosoma cruzi Infection: Adjuvant and Antigenic Effects of Heterologous T. rangeli Booster Immunization. Frontiers in immunology. 2019; 10; 1456. [PubMed: 31293599].