©2008 Global HIV Vaccine Enterprise

An HIV Vaccine:

Where Do We Go From Here?Dr. Alan Bernstein

Monday August 4, 2008

Why We Still Need an HIV Vaccine

©2008 Global HIV Vaccine Enterprise

Source: UNAIDS, 2007

Estimated Number of Adults and Children Newly Infected with HIV, 2007

Why We Need an HIV Vaccine

©2008 Global HIV Vaccine Enterprise

• A safe and effective HIV vaccine is the most promising way to stop the spread of the AIDS pandemic

• The world needs an integrated plan to defeat HIV/AIDS that includes short, medium, and long term strategies

• Short-Term: Expand currently accepted treatment modalities

• Medium-Term: Explore promising approaches (e.g. circumcision, microbicides)

• Long-Term: A safe and effective preventative vaccine

Impact of Vaccines in the United States

©2008 Global HIV Vaccine Enterprise

Steps Towards an HIV Vaccine

1. Understand Human Immune Response to HIV

• Design clinical trials to advance understanding of innate and adaptive immune response to HIV

• Bring revolution in post-genomics research to HIV vaccine development

• Expand research on long-term nonprogressors and host immune control of viral set point

• Attract and retain next generation of vaccine researchers

Pre-Clinical Research: Non-Human Primates

2. Better Exploit NHP Models to Inform and Refine Vaccine Development

• Essential for elucidating correlates of immune protection

• Validated models advance understanding of:• HIV disease progression

• Natural Immune response

• Further develop macaque models• SIV mac239

• Novel models

©2008 Global HIV Vaccine Enterprise

Rethinking Clinical Trials

3. Shift Focus from Licensure to Research

• Move away from “home run” mentality• Need for incremental increases in understanding of immune response

• Require that future clinical research emphasize approaches that will yield insights into human immune response

• Better connection between product development and fundamental research• More collaboration: industry and researchers

• Consortium approach: • CHAVI (NIH); CAVD (Gates Foundation); Eurovac, Europrise (EU);

UK HIV Vaccine Research Consortium (Wellcome Trust); Canadian HIV Clinical Trials Network (CIHR); IAVI Consortia

©2008 Global HIV Vaccine Enterprise

Rethinking Clinical Trials

4. Develop Upstream Markers to Understand and Monitor Human Immune Response To HIV

• Viral load and clinical protection are downstream markers• Not immediately informative about mechanism or vaccine design

• Downstream markers take time

• These markers make iterative vaccine design difficult

• Upstream, mechanism-based assays are required

©2008 Global HIV Vaccine Enterprise

New Approaches: Vital to Progress

5. Bring Post Genomics Revolution to HIV Vaccine Development

• New technologies allow development of downstream markers and direct study of immune response in humans•Systems and computational biology

•RNAi technologies

•Transcriptional profiling

New Minds, New Ideas: Engines of Discovery

• Young researchers bring energy, creativity, and new approaches

• Investigators from countries most affected by HIV offer new insights and perspectives

• Researchers from other fields bring new technologies

•6. Attract Best Young Investigators

New Minds, New Ideas

©2008 Global HIV Vaccine Enterprise

Nobel Laureates 1901-2003 in Three Disciplines Stratified by Age at Time of Award-Winning Discovery

Data From: Dietrich, Arne, and Narayanan Srinivasan. 2007. The optimum age to start a revolution. Journal of Creative Behavior 41: 54-74.

“In Today’s World, Marshall Nirenberg would get his Nobel Prize before he got his first R01 grant”

– Elias ZerhouniDirector, US NIH

©2008 Global HIV Vaccine Enterprise

Young Scientists: Struggling to Enter Research

©2008 Global HIV Vaccine Enterprise

Source: Science, 2008, Vol. 319 p391

Researchers under 40 account for less than 40% of NIH Grants

Trends in Distribution of Principal Investigators Receiving NIH Grants

How Do We Attract New Researchers?

©2008 Global HIV Vaccine Enterprise

New Minds, New Ideas Satellite: Conclusions

•Change perception of HIV vaccine field from product development to cutting-edge human immunological research

•Encourage established researchers to expand mentorship of young scientists

•Capitalize on growing global health programs at major universities to engage young researchers

•Support “brick and mortar” investments in developing countries to build sustainable research infrastructure and reduce brain-drain

•Reach out to other scientific fields to bring new skills, cutting-edge technologies (e.g. systems biology) and more collaborative, interdisciplinary approaches to HIV vaccine research

The Global HIV Vaccine Enterprise

©2008 Global HIV Vaccine Enterprise

A global partnership, put together by the world’s leading funders of HIV/AIDS research, to articulate the fastest way forward to a safe and effective HIV vaccine

• Global Strategic Plan

• Neutral Convener

• Honest Broker

• Catalyst

Facilitating Collaboration

GlobalStrategic

Plan

Researchers

Funders

Industry

Convening Critical Meetings

• Nossal Workshop, New York, April 2008

• Satellite: New Minds, New Ideas, AIDS 2008, August 2008

• First Council Meeting, New York, September 2008

• Systems Biology Workshop, Princeton, October 2008

• AIDS Vaccine 2008, Cape Town, October 2008

• Science Board, Fall 2008

• New Global Strategic Plan, 2009