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

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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

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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

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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

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sites, health authorities, partners

participating communities

Scientific & Community Meetings after each clinical trial

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Licensure and prequalification

MenAfriVac® licensed by Drugs Controller General of India in December 2009

WHO prequalification awarded in June 2010

SIIL/S. Vinayak

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• 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…

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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

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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

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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

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