• 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).

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 5x10^5 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