1. HIV/AIDS & TB Jerald C. Sadoff M.D. “ Journalist to Journalist” National Press Foundation Toronto, Canada August 9 th 2006

7. 22 high-burden countries: 80% of all new TB cases 0 500 1000 1500 2000 India China Indonesia Bangladesh Nigeria Pakistan Philippines South Africa Russian Federation Ethiopia DR Congo Viet Nam Kenya UR Tanzania Brazil Thailand Myanmar Zimbabwe Uganda Cambodia Afghanistan Mozambique Estimated new TB cases ('000s)

8. Highest TB rates per capita are in Africa The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. © WHO 2002 25 to 49 50 to 99 100 to 299 < 10 10 to 24 300 or more No Estimate per 100 000 population

18. By Calmette and Guérin, 1906-1921 Invention of BCG Vaccine

21. Variable Efficacy of BCG vs. Pulmonary TB British School Children British School Children British School Children S. India (Madanapalle) USA (Georgia & Alabama) S. India (Chingleput) USA (Georgia Children) USA (Chicago Infants) Puerto Rico (Gen. Pop.) N. American Indians Brazil (Sao Paolo) Argentina (Buenos Aires) Brazil (Belo Horizonte) Cameroon (Yaounde) Canada (Manitoba Indians) Surinam (Rangoon) Sri Lanka (Colombo) Colombia (Cali) Argentina (Santa Fe) Togo (Lome) Thailand Indonesia (Jakarta) Vaccine Efficacy (%) -900 -500 -300 -100 0 20 40 60 70 80 90 Population

25. Prime Boost Strategy for Infants 14 Weeks 24 Weeks

26. Booster Strategy for Adolescents

27. Mtb antigens delivered by RNA capsid system to boost rBCG Pre-clinical PhI Q2-07 Aeras AERAS X05 Recombinant Mtb antigens 85B and 10.4 combined with adjuvant IC31 to boost BCG Pre-clinical Phase I Q2 -07 SSI/Intercell Aeras HyVac 4 (AERAS 404) Replication deficient adenovirus35 which expresses antigens 85A, 85B, and 10.4 to boost rBCG Pre-clinical Phase I Q3-06) Crucell/Aeras AERAS 402 Fusion molecule comprised of a protein from the PPE family (Rv1196), combined with an inactive serine protease Rv0125 to boost BCG Phase I Aeras/GSK M72 Recombinant BCG which over expresses antigens 85A, 85B and 10.4, rvwith endosome escape Pre-Clinical Phase I Q2-07 Aeras AERAS 403 Recombinant BCG genetically modified to over express antigen 85B Phase I UCLA/Aeras rBCG30 Description Stage Source Vaccine Aeras’ TB Vaccine Candidates Under Development

29. rBCG better then BCG in Guinea pig Protection Guinea pigs Vaccinated with Sham, BCG or rBCG30 Challenged with Live aerosolized TB White arrows point to Granulomas seen at sacrifice

30. Humoral & Cellular Immunity CD 4 T cell CD 8 T cell TH1 TH2 TH1 TH2 IFN- γ IL-2 TNF- α IL-4 B - cell antibodies DTP, Hib, Pneumococcus, Measles, Polio, Hep B, Rotavirus, HPV, Malaria TB, Malaria, HIV Will CD4’s be Enough? Do we need a balance of CD4 & CD8? What cytokine profile to we need?

31. 2011 2012 2013 2014 Phase III Infants Phase III Adolescents 2006 2007 2008 2009 2010 License, Launch & Distribute Timeline Aeras 403 prime Aeras 402 boost Phase I Is it safe in 20-40 subjects in each age group . . . Phase II Does it induce an immune response? Is it safe in 200-600 subjects: infants & adolescents ? . . . Does it induce an immune response & show some protection? (Confidence for Ph III) Is it safe in 6000-9000 infants & 10000-15000 Adol ? Does it protect against TB at a licensure standard ? Can you consistently manufacture it? Will it be used ?