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Pre - clinical studies

Pre - clinical studies. Out line:. The animal model selected to perform the preclinical studies. The protocol of vaccination Evaluating the safety, immunogenicity and efficacy of the PFP vaccine. The expect results. Guniea pig as Animal model?.

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Pre - clinical studies

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  1. Pre-clinicalstudies Out line: • The animal model selected to perform the preclinical studies. • The protocol of vaccination • Evaluating the safety, immunogenicity and efficacy of the PFP vaccine. • The expect results.

  2. Guniea pig as Animal model? • guinea pig model has been extensively used • to test vaccine candidates • This model is more susceptible to the disease • than the mouse • Has elements of pathology very similar to that • seen in humans

  3. Toxcicitystudy design • Single dose toxicity • Repeated dose toxicity • Immunotoxicty • Reproductive toxicity studies • Safty • Toxicitystudy • 4 group • 12 Hartley guineapig per group (male/female) • ~ 300 gmweight • Reproductive toxicitystudy • 2 groups • 6 female Hartley guineapig per group • ~ 500 gmweight

  4. Vaccination and challenge Protocol • Immunization route: intradermaly • ( Same route as planned for clinical trial addministration) Prime immunization: • One Dose BCG (102CFU) • Boost(s): • Ag85 A-PPE44-RV2660 (PFP) • Volume: 100 μl formulated in IC-31 as adjuvant • Challenge: • low-dose aerosol of M.tb (105 CFU)

  5. Experimental groups • BCG at day 0 • First boost 9 weeks later • Group C, received 2nd boost 3 • week later • Challenge 4 weeks after final boost • Animals bled 1 day before • challenge • 4 animals sacrificed at 1 hr, 3 & 13 • weeks after challenge BCG 1stchallenge 0 9 13 16 26 w BCG 1st 2ndchallenge 0 9 12 16 19 29 w

  6. Reproductive toxicitystudies • BCG atday 0 • Pregnancy 1 weeklater • Boost 8 weekafter BCG immunisation • Expected to deliver 2 weeksafterboost BCG 1st 0 1 8 10 w

  7. Evaluating the safety and efficacy

  8. Evaluating the safety • Survival • change in Feeding behavior • Measuring change in body weight • Maternaltoxicity • Food consumption, body weight, • Clinical observations, fertility index and gestational index

  9. Histopathologyanalysis Lung section Comparing the histopathology of the lungs of animals in diffrent groups

  10. Efficacy • Counting the bacterial load [CFU] in lung and spleen ( homogenizing the lungs and plating on nutrient agar H711, and calculating the number of colonies)

  11. Immunogenecity • Humoral immunity: IgG level • T cell population in lung and spleen • lymphocyte proliferationassayfrom spleen

  12. Expectedoutcome • No change in feedingbehaviour • No body weightloss • Fewer and smallerlesion in lungcomparing • to animalsimmunizedwith BCG • lower CFU in lung and spleen, comparing to control • group immunizedwith BCG (>105)

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