Progress and Challenges for Developing

an AIDS Vaccine

Dr Simon Noble
Editor, IAVI Report and VAX,
International AIDS Vaccine Initiative
 The World Needs an AIDS Vaccine……
¾ Over 70 million HIV infections
¾ Over 28 million AIDS deaths
¾ 39.5 million currently living with HIV/AIDS
¾ 11,000 new infections daily, 95% in developing world

A comprehensive response:
Short term
Prevent further spread of the virus
Treat those already infected
Mitigate social impacts

Long term
Create the tools necessary to end the epidemic
(drugs, diagnostics, vaccines, microbicides)

Source: UNAIDS 2004

Photos: WHO/UNAIDS
 Why An AIDS Vaccine?

HIV/AIDS pandemic requires a comprehensive response

PREVENTION must be a significant part of that response

For each person who starts antiretroviral treatment, at least six

people are newly infected with HIV

(2006 – 4.3 million new infections - 650,000 newly on ARVs)

Current prevention methods are insufficient to end the epidemic

Current treatment programs are not sustainable

Only an AIDS vaccine can end the epidemic; only historically proven
tools to end viral epidemics
What is a vaccine?

A vaccine is a substance that stimulates an immune response

that can either prevent an infection or create resistance to an
infection

It is important to note, no vaccine is 100% effective. In fact,

most vaccines are between 70% - 95% effective

HERD IMMUNITY
How An AIDS Vaccine Would Work

For people not infected with HIV

To elicit immune responses
To prevent HIV infection or
progression to AIDS
 The Ideal Vaccine

One dose, low cost

Safe and highly effective
Protective in all circumstances
Candidate vaccines are made from synthetic
pieces of HIV only

Cannot cause HIV infection or AIDS

 AIDS Vaccine Development: Scientific Challenges
HIV integrates into the host cell genome – persistent
infection, short window of opportunity before
integration

HIV infects, suppresses, and destroys key cells of

the immune system

HIV antigens required for protection remain

undefined
?
Natural immune responses do not eradicate HIV;
Limitations in the animal models for HIV/AIDS;
correlates of protective immunity remain
undefined

HIV isolates worldwide are hypervariable

AIDS vaccine efficacy trials very complex and long

(4-5 years)
 The Impact Of A Vaccine Could Be Huge
New adult HIV infections in low- and middle-income countries
by year and vaccine scenario
4,500,000

4,000,000
Total new infections
3,500,000 averted by an AIDS
Vaccine introduction vaccine between
Base
3,000,000 2015-2030

2,500,000
Low effective coverage 30% efficacy, 5.5 million
2,000,000 20% coverage
1,500,000
Medium effective coverage
50% efficacy,
1,000,000 17 million
30% coverage
500,000
High effective coverage

70% efficacy,
0
2000 2005 2010 2015 2020 2025 2030 40% coverage 28 million

Source: Stover 2006. IAVI and the Futures Group

 Vaccine R&D

Basic research to identify concepts

Applied research to design candidates
Preclinical tests in animals
Clinical trials in humans
Process engineering
 The Classical Trial Paradigm

# Volunteers

Phase I Safety Dozens

Phase II Immune responses Hundreds

(and more safety)

Phase IIB
and III Efficacy Thousands
(and more safety)
 An AIDS Vaccine is Possible

Human immune system can control HIV

infection for many years (>10)
‘Elite controllers’ are extreme example
Rare individuals are naturally resistant to HIV
infection (Exposed Seronegatives)
Experimental vaccines have protected
monkeys
Human antibodies can prevent infection in
monkeys
Recent progress towards an
AIDS vaccine
 Where Does The Global R&D Effort Stand?

Advances Limitations

More candidates in the pipeline… …yet only one fully tested for efficacy, all candidates
focused on one hypothesis = cellular immunity

More countries and scientists are involved… …but response is still insufficient in some countries
and from industry

…yet we need to invest in their capacity to stay the

Developing countries are becoming more course over the long run
active partners…

Science knowledge is growing… …but scientific challenges remain a major

impediment to progress
Countries Conducting AIDS Vaccine Trials

In 2006, 13 new phase I/II trials of preventive AIDS vaccine candidates

were started in 8 countries.
VAX Special Issue – 2006 Year in Review
 AIDS Vaccines in Clinical Trials – 2007
Phase I trials – 19 ongoing Phase II trials – 3 ongoing
Including : Including :
ADVAX-DNA ADARC,IAVI
*VRC-HIVDNA-016-00-VP NIAID, IAVI,
TBC-M4 IAVI, Therion Adeno Boost USMHRP
MVA-mBN32 Bavarian Nordic
tgAAC09 IAVI, Targeted Genetics
*GENEVAX Gag-2692 NIAID, Wyeth
DNA Boost Phase IIb trials – 1 ongoing
Phase I/II trials – 3 ongoing MRKAd5 HIV-1 Merck, NIAID

Including :
*EnvDNA+- Vaccinia St. Jude; NIAID Phase III trials – 1 ongoing
Protein Boost *ALVAC vCP1521 DoD, Thailand MOPH,
Boost gp120 NIAID, TAVEG,
ALVAC-HIV and LIPO 5 NIAID, ANRS
Sanofi, VaxGen

* Prime Boost
AIDS Vaccine Designs
AIDS Vaccine Designs, Cont.
 Fast forward to 2009-2011

Current Candidates Potential Outcome Response

Need vaccine applicable

worldwide—particularly for
High efficacy developing countries and
plan for manufacture,
• Merck Ad5 – licensing and access
Results Due in
2008-9
Low to
moderate Pursue better engineered
candidates to improve upon
• Sanofi Canarypox + efficacy response
gp120 – Results
Due in 2009

Need to explore other

Inadequate mechanisms such as broadly
or no efficacy neutralizing antibody;
mucosal responses, etc.
Challenges for Developing an
AIDS vaccine
Finding a vaccine is very complicated
Issue What it means

¾HIV hyper-variability ¾We are tackling a moving

¾Immune correlates of protection are
still unknown
Scientific ¾Clades
¾Relevant animal models are lacking
¾Clinical trials are long and costly
target
¾We have to test in people
¾Success will take time

¾Long term effort requires long term, ¾We need sustained

high level global commitment - leading political support
to action ¾We need to build private
Policy & ¾Market incentives for industry activity sector engagement
Political lacking ¾We need to optimize the
¾Ethical, regulatory, IP issues environment for safe,
¾Health systems challenges ethical trials
The Extensive Genetic Diversity of HIV
The current pipeline is inadequate

Only hypothesis currently tested in pipeline is cell-mediated immunity

The Challenges, However, Are Not Only Scientific

AIDS Vaccine and other new prevention technology research is a

marathon and not a sprint

Must have
Long term commitment & support at ALL levels
Long term financing
Engagement of Industry, who have been the only ones successful
at developing vaccines
Some of the complex, non-scientific challenges

Trial site capacity and developing country research

infrastructure

Regulatory reform: speed and risk-benefit analysis without

any safety compromise

Important role of the community and vaccine preparedness

activities

Real partnership with the South – political as well as

scientific
 Why should developing countries test
vaccines early ?

Vaccines tested in industrialized countries available in developing

countries very late

Advantages of testing vaccines simultaneously in developing

countries

available first where needed most

relevant to HIV type in the region
safety in local population known early
immune response in local population
protection known in local population
(Development - science & infrastructure)
Why the Media are Vital in the Fight Against AIDS

The media have power to bring attention that

leads to action

Accurate and humanizing coverage helps

combat stigma

The media connect general public with

lifesaving medical information
 What the Media Can Do

Report on both problems and potential solutions

Spread the word in your newsroom to make

AIDS visible—it is the story of our time

Encourage your peers at other news

organizations to do the same

You can make a difference in ending the AIDS

pandemic
 24 February 2003

Large Trial Finds AIDS Vaccine Fails to Stop

Infection

24 February 2003

AIDS vaccine appears to work

 22 April, 2006

AIDS: Think Again

3 February, 2007

Medical research trial guinea pigs contract HIV

8 Novermber, 2000

Vaccine Patent Duped Kenyan Researchers

 15 August, 2006

Future promising for AIDS vaccine: group says

21 March, 2001

India to develop AIDS vaccine

 The world can and must do more.

IAVI Mission Statement

To ensure the development of a safe, effective, accessible,
preventive HIV vaccine for use throughout the world
IAVI – the first “PDPPP”

Political will R&D Clinical Production Health & Access &

& finance trials other systems uptake

10 years old
170 staff, 5 offices (Amsterdam, Delhi, Johannesburg,
Nairobi, NY), active in 23 countries
$84 million annual budget
largest global organization solely focused on HIV
vaccine; 2nd largest program
40+ R&D partnerships
6 vaccine candidates into humans, pipeline
Trials in 12 countries
‘Integrated industrial-like model’ of R&D
Emphasis on applied research and product development
– targeting gaps and promoting rational vaccine design
Industrial project management
Policy & advocacy linked (lab bench to the G8)
Sustained commitment to developing countries
IAVI Clinical Trial Network
IAVI Laboratory Network in Sub-Saharan Africa

Uganda
Kyamulibwa Kakira Kenya
Masaka UVRI Kangemi
Rwanda KAVI
Kigali
Kilifi

Zambia Lusaka

Medunsa

Jo’Burg
Durban
South Africa
CapeTown
Site Development: BEFORE
Uganda Virus Research Institute
Site of Proposed UVRI-IAVI Lab & Clinic

<#>
 AFTER
UVRI-IAVI Lab & Clinic Entebbe, Uganda
Lab/Clinic built

Laboratory:Validated CMI
assays, GLP training

Accredited and now

BMGF/CAVD reference lab

Clinic: Multiple Phase 1 HIV vaccine trials:

Accelerated approval and accelerated
enrolment vs. historical controls

Expansion: Field sites doing incidence

and other clinical studies in preparation for
future efficacy trials

<#>
 IAVI Clinical Research Studies
May 2007
Protocol A: Sero-prevalence 6532 subjects Completed

Protocol B: Sero-incidence 5100 at-risk Ongoing

volunteers enrolled

Protocol C: Early infection studies 150 of 300 enrolled Ongoing-

Collaboration with
CHAVI
Protocol D: Reference values 2410 subjects Results to be
published 2007

Protocol E: Methods validation Completed

Protocol F: Seroepi Adeno, AAV Completed
Protocol G: Broadly Neut. Sera 1st group of donors Ongoing
identified
Protocol H: Clinical, host and viral Protocol being drafted
outcomes – acute and early HIV
infection
IAVI Satellite Symposium

Accelerating the Development of Replicating Viral

Vectors for AIDS Vaccines
Sunday, July 22, 2007
8:00 a.m. - 1:00 p.m.
The Sydney Convention & Exhibition Centre
Room: Bayside 204 A

An overview of the field of replicating viral vectors

An assessment of the current viral vectors in development
Rationale for the development of replicating viral vectors for AIDS vaccines

Key speakers include:

Dr. Ian Gust, University of Melbourne
Dr. Wayne Koff, International AIDS Vaccine Initiative
Dr. Christopher Parks, International AIDS Vaccine Initiative
Mr. Jim Ackland, Global Biosolutions
Dr. Ben Berkhout, University of Amsterdam
Dr. Linqui Zhang, Chinese Academy of Medical Sciences
Dr. Keith Peden, US Food and Drug Administration
Dr. Gary Grohmann, University of Sydney
Dr. Helen Rees, Reproductive Health Research Unit, Johannesburg, South Africa
IAVI gratefully acknowledges the support of our
donors