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Group B4 March 16, 2011 Adane Miheret, Tewodros Tariku

Preclinical evaluation of safety, efficacy, immunogenicity of a recombinant rBCG Pasteur B vaccine. Group B4 March 16, 2011 Adane Miheret, Tewodros Tariku. Pre-clinical study. Objective

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Group B4 March 16, 2011 Adane Miheret, Tewodros Tariku

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  1. Preclinical evaluation of safety, efficacy, immunogenicity of a recombinant rBCG Pasteur B vaccine Group B4 March 16, 2011 Adane Miheret, Tewodros Tariku

  2. Pre-clinical study • Objective • To assess the safety (Reactogenecity and toxicity) and tolerability of rBCG Pasteur B vaccine compared to BCG • To assess the immunogenicity of rBCG Pasteur B vaccine compared to BCG • To assess the protective efficacy of rBCG Pasteur B vaccine compared to BCG

  3. Vaccine • This rBCG, a substitute for BCG, is prophylactic vaccine is intended to be used at birth to prevent infection from Mycobacterium tuberculosis. • Source of the vaccine: PASTEUR B LAB • Vaccine composition: rBCG∆mbtB∆UreC:pfoA-85AB-PPE44-DA-1 • Vaccine reconstitution: • Vaccine dose: • 5x 105, 5x106 , 5x107cfu • Number of dose: 1 dose • Route of immunization: Subcutaneous (mice and guinea pig) and Intradermal (NHP

  4. 2. Animal studies

  5. Flow chart Vaccine (n=105/105/6) BCG (n=105/105/6) Mice, Guinea Pigs & NHP Low Medium High Dose Route of immunization Subcutaneous (mice and Guinea pig) Intradermal (NHP) • Safety (5/group) • General health • Body weight • Immunogenicity (5/group) • Luminex • Flow cytometry • Protection (5 /group) • Survival time • Pathology • Weight change • Bacterial burden TNF, IL-2, IFN-γ, IL-10, TGF-β, IL-10, IL-4

  6. 3. Safety and toxicity testing in Mice and Guinea pig rBCG Immunocompromised (SCID) mice (n=30) Sacrificed for pathological examination and check for clearance of the vaccine (spleen, lung & liver) BCG 1d 2wk 8wk 12wk 16 wk rBCG Immunocompetent Mice (n=30) BCG • follow • General health status • Weight loss • Hematology • Clinical chemistry • Histopathology rBCG Guinea pig (n=30) BCG

  7. 4. Immunogenicity studies in animal models (Mice and Guinea Pigs) 4 week Vaccine (n=15) vaccination BCG (n=15) Sacrifice mice and homogenate the spleen and collect cells • Parameters to be measured • IL-2, IFN-γ, TNF-α, IL-10, IL-4, IL-17 producing CD4 and CD8 T cells = Sacrifice time

  8. 4. Efficacy studies in animal models (Mice, Guinea Pigs and NHP) Mice &Guinea Pigs (n=120) 4 week n=5 12 week n=5 BCG (n=60) vaccine 4 week (challenge) 8 week n=5 24 week n=5 Vaccine (n=60) NHP= 6 vaccine 6 week (challenge) 24 week n=3 40 week n=3 • Parameters to be measured • Bacterial burden (lung, spleen, liver) • Histopathological examination of lung, spleen, and liver • Body weight = Sacrifice time

  9. 5. Recommendation/ Expectedoutcomes • Safety profile of the new vaccine is excellent even in immunocompromised animals. • The vaccine would be very immunogenic and elicit protective Cell Mediated Immunity (CMI) polarized to Th1 type of response. • The new vaccine would enhance survival of Guinea pig infected with high dose of H37Rv with a marked reduction in bacterial load in different organs.

  10. Thank you for your attention!

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