1. HIV Vaccine Clinical Trials: In Theory and on the Ground Prof. Omu Anzala Program Director Kenya AIDS Vaccine Initiative (KAVI) Department of Medical Microbiology University Of University Kenya 18 October 2009, Paris

2. 2 Outline Vaccine Development—from the Lab to the Clinic AIDS Vaccine Design State of The Field Clinical Trials in Kenya Challenges in AIDS Vaccine R&D Progress: Case Study on Neutralizing Antibodies

3. 3 Vaccine Development From the Lab to the Clinic Concept Vaccine design Testing Political will and finance Research and development Clinical trials ProductionHealth and other systems Access and uptake

4. 4 Vaccine Development From the Lab to the Clinic Laboratory studies Animal studies Phase I clinical trials Less than a hundred volunteers. Determine safety of the candidate vaccine. Phase II clinical trials Several hundred volunteers from low- and high-risk populations. Determine safety and immunogenicity in a larger population of people. Efficacy trials (Phase IIB/Phase III clinical trials) Determine efficacy of preventing HIV/AIDS (does the candidate vaccine prevent HIV infection? and/or delay disease progression?)

5. 5 Supportive Activities for Clinical Trials Preparations in advance of clinical trials Incidence studies Community information [Media, community reps] Advocacy Regulatory clearance During clinical trials Community advisory boards inputs DSMB reviews In parallel with clinical trials Other clinical and epi-studies, e.g. Reference ranges Neutralizing antibody consortium

6. 6 Vaccine Design

7. 7 State of the Field Trials databases – up to date. www.iavireport.org/trials-db www.clincaltrials.gov

8. 8 Clinical Trials in Kenya Kenya AIDS Vaccine Initiative (KAVI) Two study sites in Nairobi: Phase I site at KAVI-KNH Phase II/III site at KAVI-Kangemi KAVI has conducted: 4 Phase I HIV vaccine trials (DNA/MVA) One Phase II HIV vaccine trials (DNA/rAd5)

9. 9 Results of Efficacy Trials http://www.avac.org/pdf/thai_vax _anticipating_results.EN.pdf

10. 10 WHAT IT MEANS  We have to test in people (Thai trial results)  We are tackling an aggressive and fast-moving target  Success will take time  We need sustained political support  We need to build private- sector engagement  We need to optimize the environment for safe, ethical trials ISSUE  HIV integrates; short window  HIV hyper-variability; clades  Immune correlates of protection are still unknown  HIV suppresses and kills cells of the immune system  Relevant animal models are lacking  Clinical trials are long and costly  Long-term effort requires long-term, high-level global commitment— leading to action  Market incentives for industry activity lacking  Ethical, regulatory, intellectual-property issues  Health-systems challenges Scientific challenges Policy and political will Challenges in AIDS Vaccine R&D

11. 11  Vaccine safety  Selection criteria for volunteers  Possible side effects  Approvals and clearances from government  Implications of vaccine on volunteer lifestyle  Provision of insurance  Why is Kenya participating  Patent and property rights, royalties Community Concerns (Kenya) Social Challenges In the Kenya Context

12. 12 Progress: Case Study on Neutralizing Antibodies

13. 13 This is the neutralizing antibody challenge  Most licensed vaccines work by inducing the body to produce antibodies that attack the infecting virus, neutralizing most of it and enabling the immune system to clear remaining virus before the onset of disease  In the blood of certain HIV-infected individuals, scientists have identified special antibodies that are broadly neutralizing—they neutralize many of the types of HIV in circulation worldwide  An AIDS vaccine will almost certainly need to elicit a sufficient amount of these broadly neutralizing antibodies The Neutralizing Antibody Challenge

14. 14 1. Nearly 2,000 blood samples collected from HIV-positive individuals around the world IAVI Human Immunology Laboratory, London 200 50 91 81 200 238 200 215 Number of donor samples from each site Monogram Biosciences 2. Samples sent to Monogram Biosciences for neutralization screening The Antibody Project: Protocol G

15. 15 3. Screening results scored using new IAVI algorithm to identify donors of interest About 1% are “elite neutralizers” Blood samples collected About 10% are donors of interest The Antibody Project: Identifying Prospects

16. 16 4. After data review, new samples requested from donors of interest IAVI NAC at Scripps 5. Samples sent to IAVI Human Immunology Laboratory IAVI Human Immunology Laboratory, London The Antibody Project: Closing In

17. 17 IAVI Human Immunology Laboratory 6. Samples sent to four partner labs for antibody rescue—each using a different technology Theraclone Rockefeller University IAVI NAC at Scripps HuMabs Monogram* *Monogram received new samples to verify neutralization screenings The Antibody Project: Partners in the Hunt

18. 18 8. Antibodies characterized 7. Theraclone is first to find new broadly neutralizing antibodies IAVI Neutralizing Antibody Center at AIDS Vaccine Design and Development Laboratory The Antibody Project: Discovery

19. 19 IAVI AIDS Vaccine Design and Development Lab IAVI Neutralizing Antibody Center at the Scripps Research Institute IAVI Human Immunology Lab Neutralizing Antibody Consortium members 9. With antibodies characterized, IAVI’s immunogen design partners take over Strand Life Sciences Elevation Biotech Chembiotek IAVI Innovation Fund recipients Lipoxen Pepscan ProSci Avatar The Antibody Project: Next Steps

20. 20 Chennai Pune Kilifi Rustenburg Cape Town Lusaka Copperbelt Kigali Masaka Entebbe Nairobi 10. Ultimately, the process comes full circle with clinical testing of vaccine candidates IAVI-supported network of clinical research centers The Antibody Project: The Return

21. 21 Questions?

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