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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
3
Viral envelope
gp41
b12
2G12
2F54E10/Z13
CD4
gp120
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=2000Adults infected with HIV at least 3 yearsWithout advanced diseaseNot on ARTNon-B clades prioritized
6
1. Nearly 2,000 blood samples collected from HIV-positive individuals around the world
IAVI Human Immunology Laboratory, London
200
50
91
81
200
200
200
200238
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
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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
IAVINAC 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
RockefellerUniversity
IAVINACat 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-supportednetworkof clinicalresearch centers
The Antibody Project: The Return