Dr Marie-Pierre Preziosi's presentation at Meningitis Research Foundation's 2013 conference, Meningitis & Septicaemia in Children & Adults http://www.meningitis.org/conference2013

1. Elimination of meningitis A epidemics in Africa
MenAfriVac future plans
Meningitis & Septicaemia in Children and Adults 2013, ninth conference Meningitis
Research Foundation, Royal Society of Medicine, London 5th November 2013
Marie-Pierre Preziosi

2. The Meningitis Vaccine Project (MVP)
A successful vaccine development for Africa

An exemplary partnership with the critical role of a developing
country vaccine manufacturer
•
State-of-the-art development of an affordable vaccine
designed to address an unmet major public health need in Africa
•
Diligent registration on this new vaccine
•
A 0-year period from vaccine licensure to introduction
at public-health scale
•
Development of a strong international scientific network
2
2

3. Epidemic meningitis in Africa: 1948-2012
3
3

4. Epidemic meningitis: impact on families

More than 10 percent of
patients die, typically
within 24-48 hours of the
onset of symptoms
 25% of survivors have
long-term aftereffects
 Expenditures of 3 to 4
months of disposable
income
PATH/Monique Berlier
Source: WHO, Colombini A, Batiano F, Zongo, S, et al. Costs for households and community perception of meningitis epidemics in Burkina Faso. Clinical Infectious Diseases 2009;49:1520–1525.
4
4

5. Epidemic meningitis: impact on public
health



Marked seasonality with
periodic devastating
epidemics
Overwhelms health
infrastructures and
disrupts routine programs
Greater than 80%
serogroup A
WHO/Kader Konde
5
5

6. The Meningitis Vaccine Project (MVP)
Early development

June 2001: Bill & Melinda Gates Foundation funds MVP
•
•

Partnership between WHO and PATH
Goal of eliminating epidemic meningitis as a public health problem
in sub-Saharan Africa through the development, testing, licensure, and
widespread use of conjugate meningococcal vaccines
2001–2002: Project constraints, African public health officials emphasize
the key importance of a low vaccine price for a sustainable supply
6
6

7. MenA vaccine development
Group A polysaccharide
produced by SynCo
BioPartners, Amsterdam.
Technology then transferred
to SIIL
Men A
polysaccharide
Serum Institute of
core team
India (SIIL) process
development and Tetanus toxoid
process development
manufacturing
manufacturing
Conjugation method
developed at CBER/
FDA, Bethesda, USA
; transferred and
scaled-up at SIIL
Conjugation
method
Target price US$ <0.50/dose
7
7

8. The Meningitis Vaccine Project (MVP)
Preparation and characterization of a meningococcal conjugate vaccine
• PsA-TT
 Ps = menA polysaccharide conjugated to a protein carrier
 TT = tetanus Toxoid
Source: Lee CH, Kuo WC, Beri S, et al. Preparation and characterization of an immunogenic meningococcal group A conjugate vaccine for use in Africa. Vaccine 2009;27:726-32.
 Vaccine development according to international standards
8
8
8

9. Vaccine Clinical development
GCP Regulatory Inspections of trial sites
9
9
9

10. Immune response in 1-29 year-olds
PsA Vaccine*
PsA-TT Vaccine
Pre
Post
Group A rSBA Geometric Mean Titers (GMT) with 95%CI
Pre-vaccination and 28 days after immunization in 5 clinical trials
Pre
Post
100 000
10 000
1 000
100
10
1
V1
V1
V3
V3
V1
V1
V3
V3
V1
V1
V3
V3
V1
V1
V3
V3
V1
V1
V3
V3
V1
V1
V3
V3
V1
V1
V1
V1
V3
V3
V3
V3
PsA-PsACWY
PsA-PsACWY
PsA-PsACWY
PsA-PsACWY
PsA-PsACWY
PsA-PsACWY
PsA-PsACWY
PsA-PsACWY
PsA-PsACWY
PsA-PsACWY
PsA- PsAC PsA- PsAC PsA- PsA- PsA- PsAC PsA- PsA- PsA- PsAC
TT
TT
TT
TT
TT
TT
TT
TT
TT
TT
TT
TT
TT
TT
TT
TT
TT
TT
Lot A Lot B Lot C
Lot A Lot B Lot C
12-23 months
2-10 years
2-10 years
11-17 years
18-29 years
18-35 years
5-10 years
PsA-TT-002
PsA-TT-003a
PsA-TT-003
PsA-TT-003
PsA-TT-003
PsA-TT-001
PsA-TT-005
10
* For all studies, reference was a PsACWY Vaccine (Mencevax®), except for study PsA-TT-001 and PsA-TT-005, where the reference vaccine was a PsAC vaccine
(Menomune® and MenA+C®, respectively)
10

11. Scientific & Community Meetings
after each clinical trial
sites, health authorities, partners
participating communities
11
11
11

12. Licensure and prequalification

MenAfriVac® licensed by Drugs Controller General of
India in December 2009
 WHO prequalification awarded in June 2010
SIIL/S. Vinayak
12
12

13. MenAfriVac introduction
Strategy
•
Inducing strong herd immunity

•
Protecting new birth cohorts

•
single dose mass vaccinations in 1–29 year-olds, with high coverage
in 26 meningitis belt countries
periodic follow-up campaigns or routine EPI immunization
Enhancing surveillance and epidemic response

throughout vaccine introduction and beyond
13
13

14. PATH/ Gabe Bienczycki
Official launch day – health workers
14
14

15. PATH/ Gabe Bienczycki
Official launch day – school children
15
15

16. MenAfriVac rollout 2010–2016
as of 5th November 2013
16
16

17. 100 000 000th vaccination
WHO/Bachir
Cotonou, Benin, 15 November 2012
17
17
17

18. Sustainable Men disease elimination: next steps
setting the scene post 2014 when the MVP project formally ends
Setting impact evaluation framework
Launching routine EPI
December 2014
October 2015
Completing roll-out
Surveillance
Specific surveys (sero, carriage, …)
Vaccine efficacy
Policy evaluation
Epidemics containment
Next generation multivalent vaccines
…
Licence for new indication
Policy
Forecasting
Country planning
Country advocacy
Sustainable fiscal space in countries
…
December 2016
Risk assessment in remaining countries
Forecasting
Procurement
Funding, GAVI Applications
Planning
Evaluating
…
18
18

19. MenAfriVac (PsA-TT) Pediatric Variation
Objectives

Rationale
• To provide a sustainable strategy to maintain population immunity
in African meningitis belt countries following the initial mass
vaccination campaigns with MenAfriVac among 1 to 29 year-olds,
by routine immunization of new birth cohorts

Questions of interest
• Immunization schedules (age, number of doses)
• Vaccine dosage
• Concomitant administrations
19
19

20. Immune response and persistence in infants
Vaccinations
at age
14-18 weeks
at age
9 months
at age
12-18 months
Group A Serum Bactericidal Antibody Titres (rSBA) GMT (95%CI) from 14 weeks to 36 months of age, Ghana
20
20

21. Immune persistence in older age groups
Reverse cumulative distribution curves in Group A specific IgG Geometric Mean Concentrations for PsATT-003 subjects by vaccine at 4 years after a single immunization (1d, n=181 ; 3d, n=86)
100%
90%
80%
60%
50%
40%
Reverse cumulative distribution curves in Men A rSBA Geometric Mean Titers for PsA-TT-003 subjects by
vaccine after a single immunization (1d, n=181 ; 3d, n=86)
30%
100%
20%
90%
10%
80%
1000
0%
0.1
1
10
100
Group A specific IgG Geometric Mean Concentrations (logarithmic scale)
Persistence - 1d - PsA-TT at 2-10 years - Four years after
Persistence - 3d - PsACWY at 2-10 years - Four years after
70%
Percentage of subjects
Percentage of subjects
70%
60%
50%
40%
30%
20%
10%
0%
2
4
8
16
32
64
128
256
512
1024
2048
4096
8192
16384
32768
65536
131072
Men A rSBA Geometric Mean Titers (logarithmic scale)
Persistence - 1d - PsA-TT at 2-10 years - Four years after
Persistence - 3d - PsACWY at 2-10 years - Four years after
21
21

22. Key considerations for the next future

Determination of the following components
•
Optimal routine schedules ?


•
Target population for routine ?

•
national or subnational
Target population for an initial catch-up campaign ?


One or two EPI doses
Supplemental periodic campaigns for low coverage districts
For cohorts missed since the mass campaign
Development of routine introduction plans that will
•
•
Promote overall enhancement of routine vaccination activities
Consider routine introduction of other new vaccines
22
22

23. AARSH
Recherche en Santé
Humaine
In collaboration with health authorities of 26 countries in sub-Saharan Africa and of India23 23

24. 24
24