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

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HIV Life Cycle & Vaccine Design

Cell Mediated Immunity

Neutralizing Antibodies

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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

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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

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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

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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

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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

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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

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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

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Progress: Case Study on Neutralizing Antibodies

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Taking the lead

Paradigm shift.

Trans-disciplinary

To achieve this international global network

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Questions?

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