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Vaccine Detail

recombinant S. typhimurium secreting M. tuberculosis ESAT-6
Vaccine Information
  • Vaccine Name: recombinant S. typhimurium secreting M. tuberculosis ESAT-6
  • Target Pathogen: Mycobacterium tuberculosis
  • Target Disease: Tuberculosis
  • Vaccine Ontology ID: VO_0000535
  • Type: Live, attenuated vaccine
  • Antigen: ESAT-6 of Mycobacterium tuberculosis (Mollenkopf et al., 2001). ESAT-6 can induce IFN-gamma production and activate T cells in human peripheral blood mononuclear cells in TB patients.
  • EsxA (ESAT-6) gene engineering:
    • Type: Fusion protein with adjuvant
    • Description:
    • Detailed Gene Information: Click Here.
  • Preparation: This vaccine utilizes an attenuated Salmonella typhimurium that secretes a T-cell antigen called ESAT-6 of Mycobacterium tuberculosis through the hemolysin secretion system of E. coli (Mollenkopf et al., 2001).
  • Description: ESAT-6 has been tested as a skin-test reagent in cattle and guinea pigs. The subunit vaccine which combines ESAT-6 with monophosphoryl lipid A (MPL) and dimethyl dioctadecylammonium bromide (DDA) was developed and tested for use in BALB/c female mice (Mollenkopf et al., 2001).
Host Response

Mouse Response

  • Host Strain: BALB/c, female
  • Vaccination Protocol: Recombinant S. typhimurium was injected into tail vein of each mouse and cured with10 mg ampicillin injected intraperitoneally (i.p.). Five mice used per group. Group A received high-dose vaccine 90 days pre-challenge and was cured twice with ampicillin. Group B received low-dose recombinant vaccine 60 days pre-challenge. Group C was vaccinated at 90, 60, and 30 days pre-challenge. Group D received s.i. prime with bacteria and naked DNA 90 days pre-challenge, two DNA boosts at 60 and 30 days pre-challenge, and curing twice. Group E received the same vaccinations and challenges as in D, though in a different order. GeneGun and pcDNAesat or PIRESesat were used during vaccination (Mollenkopf et al., 2001).
  • Persistence:
  • Side Effects: Spleens were enlarged after procedure, though CFU analysis revealed that the mice were free of Salmonella bacteria (Mollenkopf et al., 2001).
  • Challenge Protocol: Challenge route was same as in vaccination (tail vein injection), though employed 5x105 CFUs of the virulent M. tuberculosis H37Rv i.v. (Mollenkopf et al., 2001)
  • Efficacy: A significant difference in colony-forming units was seen at 10 versus 60 days post challenge (Mollenkopf et al., 2001). S. typhimurium induced a small but signifcant degree of protection in lungs, though only small degree of protection in the liver at day 60 (Mollenkopf et al., 2001).
  • Information about this animal model: Mouse Model for TB research
References
Mollenkopf et al., 2001: Mollenkopf HJ, Groine-Triebkorn D, Andersen P, Hess J, Kaufmann SH. Protective efficacy against tuberculosis of ESAT-6 secreted by a live Salmonella typhimurium vaccine carrier strain and expressed by naked DNA. Vaccine. 2001 Jul 16; 19(28-29); 4028-35. [PubMed: 11427279].