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Discovery of New Antibodies Against HIV A Case Study of a Global Partnership

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. Neutralizing Antibodies. Cell Mediated Immunity.

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Discovery of New Antibodies Against HIV A Case Study of a Global Partnership

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  1. Discovery of New Antibodies Against HIVA 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. Neutralizing Antibodies Cell Mediated Immunity HIV Life Cycle & Vaccine Design

  3. 2G12 CD4 b12 gp120 2F5 gp41 4E10/Z13 Viral envelope 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 • This is 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. The Antibody Project: Protocol G IAVI Human Immunology Laboratory, London Monogram Biosciences 50 91 81 200 200 200 200 238 200 215 200 Number of donor samples from each site 1. Nearly 2,000 blood samples collected from HIV-positive individuals around the world 2. Samples sent to Monogram Biosciences for neutralization screening

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

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

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

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

  11. Progress: Case Study on Neutralizing Antibodies

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

  13. Questions?

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