Transcript The status of progress towards new TB vaccines

The status of progress
towards new TB
vaccines
Hassan Mahomed
South African Tuberculosis Vaccine Initiative,
University of Cape Town but also on behalf of the
Aeras Global Tuberculosis Vaccine Foundation,
Rockville, Maryland, U.S.A
Background
Tuberculosis (TB) is a major global public
health problem with 8.9 million new cases
in 2004 affecting mainly Africa, South-East
Asia and the Western Pacific (WHO).
 One third of the world’s population is
estimated to be infected with the
tuberculosis mycobacterium.
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Source: WHO report 2006: Global Tuberculosis Control
The Top 10 high burden TB
countries
Country
Population
1000’s
All TB cases
1000’s
TB cases per
100 000
1.India
1 087 124
1824
168
2. China
1 307 989
1325
101
3. Indonesia
220 077
539
245
4. Nigeria
128 709
374
290
5. South Africa
47 208
339
718
6. Bangladesh
139 215
319
229
7. Pakistan
154 794
281
181
8. Ethiopia
75 600
267
353
9. Phillipines
81 617
239
293
10. Kenya
33 467
207
619
Source: WHO report 2006: Global Tuberculosis Control
2002: Most TB cases were in India and China
India – 1.75 M Cases
Europe 10%
China – 1.33 M Cases
Number of cases
< 1 000
1 000 - 9 999
10 000 - 99 999
100 000 - 999 999
1 000 000 or more
No estimate
Africa
21%
Asia
59%
The designations employed and the presentation of material on this map do not imply the expression of any opinion whatsoever on the part of the
World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its
frontiers or boundaries. White lines on maps represent approximate border lines for which there may not yet be full agreement.
© WHO 2003
Global Tuberculosis Control. WHO Report 2003. WHO/HTM/TB/2004.331
Highest TB rates per capita are in Africa
per 100 000 population
< 10
10 to 24
25 to 49
50 to 99
100 to 299
300 or more
No Estimate
TB and HIV
55% of South Africans with TB also have
HIV.
 TB is the most common cause of death in
people living with HIV.
 Those living with HIV have a 10% annual
risk of contracting TB.
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What is a vaccine?
A vaccine is made from an infectious
organism but modified either by
weakening it or by taking a piece of it.
 This is then given either by injection or
orally or by a novel method e.g. aerosol.
 The body’s immune response to this is
intended to protect against infection and
disease caused by the infectious organism
itself.
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Vaccine success stories
Small pox eradication.
 Polio close to eradication.
 Also, measles, diphtheria, whooping
cough and many others.
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TB vaccination
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Bacille Calmette Guérin (BCG) has been around
since the 1920s.
It is the mostly widely used vaccination today
(about 100 million doses in 2002).
However, its efficacy is controversial.
Nevertheless, there is broad consensus that it
provides protection against severe forms of
childhood TB.
Unfortunately, there is growing concern that
BCG can cause disease in HIV infected infants.
Prospects for new vaccines:
approaches
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Replacement of BCG by a more potent pre-exposure
vaccination inducing an immune response capable
either of
 complete elimination of all of the infecting organisms,
or
 reliable containment of persistent infection.
Postexposure vaccination to boost immunity in
individuals whose natural immune response has already
been primed by infection or by BCG vaccination.
Target in both cases: enhancement of BCG / natural
immunity.
Aeras Global TB Vaccine
Foundation
Is an: International non-profit Product Development
Partnership (PDP) funded by foundations (Bill & Melinda
Gates) and government (DANIDA, CDC, NIH) that
partners with industry and academia to develop high risk,
high volume, low profit but desperately needed new TB
vaccines.
Mission: To develop new TB vaccines and ensure their
availability to all who need them
Goals:
- To obtain regulatory approval and ensure supply of a
new TB vaccine regimen within 7-10 years
- To introduce 2nd generation vaccines with improved
product profiles and efficacy against latent TB in 9-15
years
A Promising Pipeline of Candidates
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Recombinant BCG
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Aeras
MPI/VPM
Aeras
Recombinant fusion proteins in adjuvant
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rBCG30 (well tolerated in phase I)
Endosome escaping rBCG
Aeras 412
Mtb72f/M72 fusion (well tolerated in phase I)
Ag85B::ESAT6
Ag85B::10.4 fusion
GSK
SSI/TBVAC
SSI/Aeras
Vectored vaccines
rMVA-Ag85A (well tolerated in many Phase I)
 rAd35-Ag85A::Ag85B::TB-Y fusion
 Oral Shigella dsRNA
Bold type indicates Aeras support
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Oxford
Aeras/Crucell
Aeras
TB vaccine candidates currently in
human trials
MVA85A (University of Oxford, UK)
 rBCG30 (St Louis University, US)
 Mtb72F (Corixacorp, US)
 Hybrid-1 (85B-ESAT6) (SSI, Denmark)
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The role of the community
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Community advocacy for new TB vaccines
Increase community knowledge about the value
of vaccines.
Participate in research Community Advisory
Boards.
Support research initiatives but also monitor
study processes.
Particularly look after participant interests.
Site development
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South African Tuberculosis Vaccine Initiative –
Worcester/ Boland trial site
India – Palamaner/ Institute for Population
Health and Clinical Research, Bangalore
EDCTP - Uganda and/or Kenya and/or Senegal
Infrastructure, skills development,
epidemiological baseline studies.
Professional Development Programme
Critical Success factors
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Community Advocacy
Promising candidates
Basic science development capacity
Clinical Trial Field Site infrastructure
Demonstrated phase 1 and 2 safety including for
those infected with HIV.
Demonstrated efficacy
Large scale production capacity
Affordability
Distribution infrastructure
Health care infra-structure
Conclusions
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There is a high global TB burden.
The existing vaccine, BCG has variable efficacy.
A number of new TB vaccines are coming
through the “pipeline”.
The Aeras pipeline aims to produce a successful
vaccine by 2012.
The community has a crucial role to play in
supporting the development of a new TB
vaccine.
By 2015, we will hopefully have in use a new,
affordable and effective TB vaccine.
Acknowledgements
Aeras Global TB Vaccine Foundation (Dr L
Geiter)
 Dr T Hawkridge (SATVI) and other staff
members of the team.
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