elimination of meningitis a epidemics in africa; menafrivac future plans
DESCRIPTION
Dr Marie-Pierre Preziosi's presentation at Meningitis Research Foundation's 2013 conference, Meningitis & Septicaemia in Children & Adults http://www.meningitis.org/conference2013TRANSCRIPT
Elimination of meningitis A epidemics in Africa MenAfriVac future plansMeningitis & Septicaemia in Children and Adults 2013, ninth conference Meningitis Research Foundation, Royal Society of Medicine, London 5th November 2013
Marie-Pierre Preziosi
22
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
The Meningitis Vaccine Project (MVP)A successful vaccine development for Africa
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Epidemic meningitis in Africa: 1948-2012
44
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
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.
PATH/Monique Berlier
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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
66
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
77
MenA vaccine development
core team
Tetanus toxoidprocess development
manufacturing
Men A polysaccharide
Conjugationmethod
Target price US$ <0.50/dose
Group A polysaccharide produced by SynCo BioPartners, Amsterdam. Technology then transferred to SIIL
Conjugation method developed at CBER/ FDA, Bethesda, USA; transferred and scaled-up at SIIL
Serum Institute of India (SIIL) process development and manufacturing
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• PsA-TT Ps = menA polysaccharide conjugated to a protein carrier TT = tetanus Toxoid
Vaccine development according to international standards
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.
The Meningitis Vaccine Project (MVP)Preparation and characterization of a meningococcal conjugate vaccine
999
Vaccine Clinical developmentGCP Regulatory Inspections of trial sites
1010* 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)
Group A rSBA Geometric Mean Titers (GMT) with 95%CI Pre-vaccination and 28 days after immunization in 5 clinical trials
Pre
Post
PsA-TT Vaccine
Pre
Post
PsA Vaccine*
1
10
100
1 000
10 000
100 000
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-TT
PsACWYPsA-TT
PsACWYPsA-TT
PsACWYPsA-TT
PsACWYPsA-TT
PsACWYPsA-TT
PsACWYPsA-TT
PsACWYPsA-TT
PsACWYPsA-TT
PsACWYPsA-TT
PsACWYPsA-TT
PsAC PsA-TT
PsAC PsA-TT
Lot A
PsA-TT
Lot B
PsA-TT
Lot C
PsAC PsA-TT
Lot A
PsA-TT
Lot B
PsA-TT
Lot C
PsAC
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
Immune response in 1-29 year-olds
111111
sites, health authorities, partners
participating communities
Scientific & Community Meetings after each clinical trial
1212
Licensure and prequalification
MenAfriVac® licensed by Drugs Controller General of India in December 2009
WHO prequalification awarded in June 2010
SIIL/S. Vinayak
1313
• Inducing strong herd immunity single dose mass vaccinations in 1–29 year-olds, with high coverage
in 26 meningitis belt countries
• Protecting new birth cohorts periodic follow-up campaigns or routine EPI immunization
• Enhancing surveillance and epidemic response throughout vaccine introduction and beyond
MenAfriVac introductionStrategy
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Official launch day – health workers
PATH
/ G
abe
Bien
czyc
ki
1515
Official launch day – school children
PATH
/ G
abe
Bien
czyc
ki
1616
MenAfriVac rollout 2010–2016 as of 5th November 2013
171717
100 000 000th vaccinationCotonou, Benin, 15 November 2012
WH
O/B
achi
r
1818
Sustainable Men disease elimination: next stepssetting the scene post 2014 when the MVP project formally ends
Setting impact evaluation framework
December 2014
SurveillanceSpecific surveys (sero, carriage, …)Vaccine efficacy Policy evaluationEpidemics containmentNext generation multivalent vaccines …
Launching routine EPI
October 2015
Licence for new indicationPolicyForecastingCountry planning Country advocacySustainable fiscal space in countries…
Completing roll-out
December 2016
Risk assessment in remaining countries ForecastingProcurementFunding, GAVI ApplicationsPlanningEvaluating…
1919
MenAfriVac (PsA-TT) Pediatric VariationObjectives
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
2020
Vaccinations
at age 14-18 weeks
at age 9 months
at age 12-18 months
Immune response and persistence in infants
Group A Serum Bactericidal Antibody Titres (rSBA) GMT (95%CI) from 14 weeks to 36 months of age, Ghana
2121
Immune persistence in older age groups
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0.1 1 10 100 1000
Perc
enta
ge o
f sub
ject
s
Group A specific IgG Geometric Mean Concentrations (logarithmic scale)
Reverse cumulative distribution curves in Group A specific IgG Geometric Mean Concentrations for PsA-TT-003 subjects by vaccine at 4 years after a single immunization (1d, n=181 ; 3d, n=86)
Persistence - 1d - PsA-TT at 2-10 years - Four years after
Persistence - 3d - PsACWY at 2-10 years - Four years after
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2 4 8 16 32 64 128 256 512 1024 2048 4096 8192 16384 32768 65536 131072
Perc
enta
ge o
f sub
ject
s
Men A rSBA Geometric Mean Titers (logarithmic scale)
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)
Persistence - 1d - PsA-TT at 2-10 years - Four years after
Persistence - 3d - PsACWY at 2-10 years - Four years after
2222
Determination of the following components • Optimal routine schedules ?
One or two EPI doses Supplemental periodic campaigns for low coverage districts
• Target population for routine ? national or subnational
• Target population for an initial catch-up campaign ? 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
Key considerations for the next future
2323
AARSH
Recherche en Santé Humaine
In collaboration with health authorities of 26 countries in sub-Saharan Africa and of India
2424