1. Malaria Vaccines: What we need for success
[Acknowledge Stephen O’Brien, other distinguished guests]
Good afternoon.
Thank you for invitation
BACKGROUND INFORMATION:
Chairman: Stephen O’Brien MP (Conservative)
Vice-Chairman: Dr Ian Gibson MP (Labour)
Vice Chairman: Lord Rea (Labour)
Vice-Chairman: Dr Evan Harris MP (Lib-Dem)
Vice Chairman: David Drew MP (Labour)
Treasurer: Ashok Kumar MP (Labour)
Secretary: Eleanor Laing MP (Conservative)
Coordinator: Susan Dykes
Christian Loucq, MD
Director, PATH Malaria Vaccine Initiative
8 July 2008
UK All-Party Parliamentary Malaria Group

2. Why I’m Here: To Answer Three Questions
What is the PATH Malaria Vaccine Initiative (MVI)?
Why a vaccine?
What will it take?
Why I am here today:
To share my hope and excitement
To answer three questions:
What is MVI?
Why a vaccine?
What will it take?

3. A world free from malaria
To accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world
What is MVI?
Our mission
Our vision
Focus: the parasite lifecycle
One of three goals: a vaccine for infants and young children
A world free from malaria
Founded in 1999
Donors: Bill & Melinda Gates Foundation US Agency for International Development,
ExxonMobil, private individuals

4. A world free from malaria
To accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world
Availability:
Global access
Regulatory & policy pathways
Accessibility:
Preparing countries for the vaccine introduction
Decision-making framework
Two other goals (from development to DELIVERY):
Availability: licensed for use, financed,
Accessibility: adopted by countries, integrated into existing systems
How we work:
Vaccine INVESTOR
Partnerships
Collaboration: Global Vaccine Portfolio
A world free from malaria

5. MVI: A global program of PATH
WHAT IS MVI?
A global program of PATH:
International health NGO
Track record of SUCCESSFUL vaccine development

6. Why a Malaria Vaccine? Why a vaccine?
HISTORICALLY: Most efficient way to prevent disease
TODAY (Version 1.0 in 2012):
A partially effective vaccine will reduce deaths and illnesses
TOMORROW (Version 2.0 by 2025):
An 80% effective vaccine will help ERADICATE malaria
PHOTOS
Salim with sick child (malaria)
Girl with vaccination card (let’s add malaria to the list)

7. Why a Malaria Vaccine? Age Distribution of Severe Malaria
0.14
0.12
0.1
0.08
0.06
0.04
0.02
Gupta et al., Nature Medicine 5: , 1999
Sukuta
Kalifi N
Kalifi S
Siaya
Proportion Affected
Why a Vaccine?
Infants at most risk
Under-Fives altogether
Pregnant women come next
In Kintampo, Ghana, where one of our partner trial sites is located, each person is bitten – on average – 300 times each year by infected mosquitoes.
1-2
mos
3-4
mos
5-6
mos
6-12
mos
Age group 7

8. Targeting the Parasite Lifecycle
If the vaccine targets….
Its goal is to….
Pre-erythrocytic Stage
Prevent infection
Blood-stage
Reduce clinical disease
Sexual transmission blocking
Prevent the spread of parasites by mosquitoes
THE ‘NEXT GENERATION’ GOAL
80 PERCENT
HOW DO WE GET THERE?
Target different stages
Explore different approaches
Combine them together

9. Research and Development Strategy
HOW DO WE GET THERE?
Robust strategy
Exciting advances
Strong partners from discovery, through development AND delivery
KEY ELEMENTS (EXPLAIN)
New antigens
New platforms
New adjuvants and mixtures
Evaluation technologies
BACKGROUND
Antigen: manipulate protein in lab so body thinks it is the real thing
Platform: targeted delivery vehicle
Adjuvant: clean dirt (chemical)
Evaluation: assess effect BEFORE human test

10. Product Candidates Research Programs Targets P. vivax Pre-erythroctyic
Construct
Selection
Process
Development
Final
Formulation
Toxicology
Phase 1a
Phase 1/2a
Phase 1b
Phase 2b
Sanaria
PfSPZ
GSK
RTS,S
AS01/AS02
Product Candidates
Targets
P. vivax
Pre-erythroctyic
(liver)
Pre-erythroctyic
(liver)
ICGEB/BBIL
PvRII
Monash
MSP4
GenVec
Ad5-CSP:
LSA1:Ag2 +
Ad5-MSP1:
AMA1
LaTrobe
MSP2
ISA720
WHAT DO WE HAVE TODAY (EXPLAIN)
Potential products
Research programs
Blood-stage
MVDB
AMA1-C1
ISA720
Research Programs
Adjuvanted Recombinant Proteins
Viral Vectored
Live Attenuated (weakened)
WRAIR/GSK
AMA1
AS01/AS02

11. RTS,S Clinical Research Center Network
IRSS - Centre Muraz
KHRC, Kintampo
KCCR, Kumasi
KEMRI - Kisumu
HAS, Lambarene
KEMRI - Kilifi
JMP, Korogwe
IHDRC, Bagamoyo
KCH, Lilongwe
RTS,S: Closest to use
First-ever Phase 3
Early development by GSK Biologicals and US Walter Reed Army Institute of Research
Network of 10 trial sites (11 facilities) in 7 countries
NEED Phase 3 to assess efficacy in diverse settings.
BACKGROUND:
Burkina Faso, Gabon, Ghana (2), Kenya (2/3), Malawi, Mozambique, and Tanzania (2)].
CISM, Manhiça
RTS,S MVI-GSK Program in Africa

12. WHO Vaccine Prioritization Vaccines that may be licensed by 2012 (WHO SAGE, November 2007)
WHY a partially effective vaccine?
The whole world cares:
Top bar, LONGEST, is malaria
Many endemic countries want it:
SAVE hundreds of thousands of lives
Weighted priority score based upon expert opinion

13. Sanaria: A Different Approach
Targets the whole parasite
Uses a live, attenuated parasite
ANOTHER APPROACH (version 2.0????)
Harvest sporozoites from salivary glands of irradiated mosquitoes
DISSECT (die-sect)
Nussenzweigs and Vandenberg
Human trial in early 2009

14. Challenges: What will it take?
No vaccine against a parasite
No known correlates of immunity
No “market”
CHALLENGES to DELIVERING vaccines:
Scientific: 6,000 proteins
Business: No market (in traditional terms)
Financial: Expensive (half billion dollars)
Political: Long-term commitment is needed (especially by donors)

15. What will it take? Strong partners
Strong, committed partners will make it happen
SCIENTISTS, like Salim in this picture
BUSINESSES, like GSK Biologicals, Sanaria, GenVec
PARENTS, who volunteer their kids
POLICYMAKERS, making informed decisions
DONORS, like the Gates Foundation, but WE NEED OTHERS

16. What will it take? Sustained commitment
To OVERCOME malaria, we need SUSTAINED COMMITMENT
YOU can help by adding your voices….
Expand existing interventions
AND make them better
Invest in new tools, VACCINES
Push AND Pull

17. Partners Today … and Tomorrow
Key partners in the development and delivery of vaccines
DFID and the UK government have already made a difference
NEW research strategy is promising
PUSH and PULL funding are both needed

18. What can you do? Support investments in malaria control today
Advocate now for investments in the tools for tomorrow
And …