Status of Malaria Vaccine

Development Worldwide
Ministry of Health, Government of Ethiopia
Vaccine Development Pathway

At least ten years and > $500 million to develop a

vaccine from the production to manufacture and supply
1. Production/formulation

2. Laboratory animal studies –

safety, efficacy

3. Clinical Trials in Adults then

Children – Safety, Efficacy

4. Manufacture and supply product

 Stages of a Vaccine Clinical
Development Program

Phase I Phase II Phase III Phase IV

Type of Trial Proof of Principle Dose Ranging Pivotal Licensure Postmarketing

Scheduling Studies Studies
Preliminary
Efficacy
Endpoints Safety Safety Safety Safety
Immunogenicity Immunogenicity Immunogenicity Surveillance
Efficacy in Efficacy Secondary
Malaria Trials Endpoints
Effectiveness

Typical 10s 100s Endpoint specific Endpoint specific

Sample Size (10,000-50,000) 10,000
Malaria Vaccines Are Feasible

Weakened parasites Protection from infection

Long-term natural exposure Protection from

clinical disease

Transfusion of antibody Impact disease

Malaria Vaccines: Stages and Impact

Pre-erythrocytic
Vaccines to prevent infection
and impact disease

Blood Stage
Vaccines to lessen disease

Transmission Blocking
Vaccines to prevent transmission
Malaria Vaccine Technology Roadmap

Strategic Goal
• By 2025, develop and license a malaria vaccine that has a
protective efficacy of more than 80% against clinical disease and
lasts longer than four years.

Milestone
• By 2015, develop and license a first-generation malaria vaccine that
has a protective efficacy of more than 50% against severe disease
and death and lasts longer than one year.
Malaria Vaccine Pipeline

• > 90 candidate vaccine concepts (WHO)

• > 50% based on a small number of antigens
(CSP, AMA1 and MSP1)
• Most concepts are in research (vs development)
• 60% are protein-based vaccines
• Number of “product like” candidates has doubled in
past 2-3 years
• Leading vaccine is RTS,S, with other vaccines many
years behind
RTS,S

Recent RTS,S Phase 2 trials

• Children ages 1-4 in Mozambique
• Conducted at Centro de Investigação em Saúde da
Manhiça (CISM)
• Nov, 2004: Over 6 month follow-up period, the
vaccine:
• reduced the risk of clinical malaria by 30%
• reduced the risk of severe malaria by 58%
• Nov, 2005: Efficacy did not wane over 18 months
• reduced clinical malaria episodes by 35%
• reduced severe malaria episodes by 49%
Alonso et al. Lancet 2004; 364: 1411–20
Alonso et al. Lancet 2005; 366: 2012–18
RTS,S Next Steps

• Additional Phase 2 trials in infants and young

children in several African countries
• Phase 2 data to inform phase 3 trial design
• Phase 3 clinical trials in at least 6 African countries
• 2010 estimated submission for licensure
• If successful, vaccine licensure and use from late
2011
FP9/MVA ME-TRAP (Oxford/Oxxon)

• Multiple UK challenge trials with ME-TRAP

(pooled N = 43)
• VE = ~23% protection with high dose regimes
• mean 40 hour extension in pre-patent period

• Kenyan pediatric clinical disease (N=410)

• VE against cumulative clinical episodes - ongoing
MSP1/AS02 ( FMP1/AS02)
(WRAIR/MVI/USAID/GSK)

• Safe and immunogenic, tested in two areas of

different malaria transmission intensity (high/western
Kenya, and low/Mali).

• Results from POC trial in pediatric population

expected anytime.
AMA 1-C1/Alhydrogel(NIH/Mali)

• Safe and immunogenic in Malian adults

• Ongoing pediatric safety trial in Malian children
before POC trial in children

• AMA1 – also being developed by other groups

• NIH – other formulations being considered
• WRAIR – AS02a completed safety in semi-immunes
• EMVI/BPRC – various formulations being compared
for safety and immunogenicity