Discovery of New Antibodies Against HIV A Case Study of a Global Partnership Prof. Omu Anzala Program Director Kenya AIDS Vaccine Initiative (KAVI) Department of Medical Microbiology University Of Nairobi Kenya

2 HIV Life Cycle & Vaccine Design Cell Mediated Immunity Neutralizing Antibodies

3 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

4 Solve the Neutralizing Antibody Problem Goal: Advance to clinical trials candidate(s) which elicit HIV-specific broadly neutralizing antibodies Broadly neutralizing antibodies against HIV exist Sera from HIV+ (4) broadly neutralizing monoclonal antibodies (bnMAbs) Vaccine design targeting binding sites for the 4 bnMAbs has thus far failed New, more potent, broadly neutralizing antibodies which target novel sites on HIV Env are needed to facilitate vaccine design

5 Protocol G - Overview Purpose: To generate novel potent and broad neutralizing monoclonal antibodies (bnMAbs) from HIV infected subjects who have broadly neutralizing serum activity Methods:Screen HIV infected individuals for broadly neutralizing serum activity Key issue: Validated screening assay Select subjects with broad and potent neutralization activity Key Issue: Cohorts in the developing world Derive bnMAbs from their PBMCs Key Issue: Multiple technologies to increase the chances of success Study population: N=2000 Adults infected with HIV at least 3 years Without advanced disease Not on ART Non-B clades prioritized

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

7 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

8 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

9 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

10 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

11 Progress: Case Study on Neutralizing Antibodies

12 Taking the lead Paradigm shift. Trans-disciplinary To achieve this international global network

13

14 Questions?

15