Hiv vaccine clinical trials in theory and on the ground
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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. Outline. Vaccine Development—from the Lab to the Clinic

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HIV Vaccine Clinical Trials: In Theory and on the Ground

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Hiv vaccine clinical trials in theory and on the ground

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


Outline

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


Vaccine development from the lab to the clinic

Vaccine DevelopmentFrom the Lab to the Clinic

  • Concept

  • Vaccine design

  • Testing

Political willand finance

Researchand development

Clinical

trials

Production

Health and other systems

Accessand uptake


Vaccine development from the lab to the clinic1

Vaccine DevelopmentFrom 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?)


Supportive activities for clinical trials

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


Hiv vaccine clinical trials in theory and on the ground

Vaccine Design


State of the field

State of the Field

  • Trials databases – up to date.

  • www.iavireport.org/trials-db

  • www.clincaltrials.gov


Clinical trials in kenya

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)


Results of efficacy trials

Results of Efficacy Trials

http://www.avac.org/pdf/thai_vax_anticipating_results.EN.pdf


Hiv vaccine clinical trials in theory and on the ground

Challenges in AIDS Vaccine R&D

ISSUE

WHAT IT MEANS

Scientific challenges

  • HIV integrates; short window

  • HIV hyper-variability; clades

  • Immune correlates of protection are still unknown

  • HIV suppresses and kills cellsof the immune system

  • Relevant animal models are lacking

  • Clinical trials are long and costly

  • We have to test in people (Thai trial results)

  • We are tackling an aggressive and fast-moving target

  • Success will take time

Policyandpolitical will

  • 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

  • We need sustained political support

  • We need to build private-sector engagement

  • We need to optimize the environment for safe, ethical trials


Hiv vaccine clinical trials in theory and on the ground

Social Challenges

In the Kenya Context

Community Concerns

(Kenya)

  • 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


Progress case study on neutralizing antibodies

Progress: Case Study on Neutralizing Antibodies


Hiv vaccine clinical trials in theory and on the ground

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


Hiv vaccine clinical trials in theory and on the ground

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


3 screening results scored using new iavi algorithm to identify donors of interest

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”


Hiv vaccine clinical trials in theory and on the ground

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


Hiv vaccine clinical trials in theory and on the ground

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


Hiv vaccine clinical trials in theory and on the ground

The Antibody Project: Discovery

7. Theraclone is firstto find new broadly neutralizing antibodies

8. Antibodies characterized

IAVI Neutralizing Antibody Center at

AIDS Vaccine Design and Development Laboratory


Hiv vaccine clinical trials in theory and on the ground

The Antibody Project: Next Steps

IAVI Human Immunology Lab

Lipoxen

Pepscan

Avatar

IAVI AIDS Vaccine Design and Development Lab

ProSci

StrandLife Sciences

Chembiotek

IAVI Neutralizing Antibody Centerat the Scripps Research Institute

Neutralizing Antibody Consortium members

Elevation Biotech

IAVI Innovation Fund recipients

9. With antibodies characterized, IAVI’s immunogen design partners take over


Hiv vaccine clinical trials in theory and on the ground

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


Hiv vaccine clinical trials in theory and on the ground

Questions?


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