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Optimising PneumococcalConjugateSchedules

ProfessorDavidGoldblattUCLGreatOrmondStreetInstituteofChildHealth

and

GreatOrmondStreetHospitalforChildrenNHSFoundationTrust

§ VaccineScheduleRefinementintheUK1990-2015§ PCVintroductionanddiseasecontrol§ Possibleapproachestooptimising PCVuse§ ResultsofaPCV2+1vs1+1Randomised ControlTrial§ GlobalPCVconsiderations

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1990 2000 2010 2015 202099 06 13

MenC3+0

MenC2+1

MenC1+1

+adol

MenC0+1

MenACWYadol

MenB2+1

Hib3+0

Hib3+1

HibBoostercampaign

Licensed3+1

PCV72+1

PCV132+1

Licensed3+1

HPV3 dose

HPV2dose

08 14

UKVaccineIntroductionandScheduleChanges

YEAR 2000 2006/7 2010/11 2013/14

UK(2+1)

USA(3+1)

PCV7IPD<2y99%reduction1

PCV7CarriageNearElimination2

PCV7IPDallages86%reduced1

13-769%2

PCV13-7IPD<289%Reduction1

PCV7IPD<5y97%3

PCV7CarriageMass.Childrennearelimination4

PCV13-7IPD<593%5

1 Waight etal2015,2 vanHoeketal2014,3 Feikin etal2013,4 Wroe etal2012,5 Mooreetal2015,6 Yildrim etal2017

PCV13-7CarrMass.ChildrenVeryLow6

ImpactofPCVIntroduction

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Invasivepneumococcaldiseaseincidence rateper100,000popn byagegrouping,E&W

1996-2005

0

10

20

30

40

50

60

70

80

<2m 2-5m 6-11 m 1 year 2-4 years 5-9 years 10-14years

15-44years

45-64years

65-74years

75-79years

80+ years

Age range

Rate

per

100,0

00 p

opul

atio

n

1996/97 1997/98

1998/99 1999/00

2000/01 2001/02

2002/03 2003/04

2004/05

DatacourtesyoftheHealthProtectionAgency

Optimising theuseofPneumococcalConjugateVaccines

PCV7TypeIPD

0.32/100,00035.78/100,000

17.73/100,000

0.55/100,000

• Australianpaper

2017

3+0 2+1

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Invasivepneumococcaldiseaseincidence rateper100,000popn byagegrouping,E&W

1996-2005

0

10

20

30

40

50

60

70

80

<2m 2-5m 6-11 m 1 year 2-4 years 5-9 years 10-14years

15-44years

45-64years

65-74years

75-79years

80+ years

Age range

Rate

per

100,0

00 p

opul

atio

n

1996/97 1997/98

1998/99 1999/00

2000/01 2001/02

2002/03 2003/04

2004/05

DatacourtesyoftheHealthProtectionAgency

Optimising theuseofPneumococcalConjugateVaccines

PCV7TypeIPD0.32/100,000

35.78/100,000

17.73/100,000

0.55/100,000

Risksofremovingthisdose?

Whitney et al. Lancet 2006;368:1495-502

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Andrews NJ et al. Lancet Infect Dis 2014;14:839-46

1dose2.5<13mVE38%(95%CI-218– 89)

Miller et al Vaccine 2011

Potential benefits of reducing the PCV schedule to 1+1

• Simplified and more acceptable infant schedule

• Possible reduced frequency of adverse events

• Creates space in the schedule for new vaccines in the future

• Cost Savings, resources saved can be used on other vaccine related interventions (eg improve coverage)

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JCVI2006:PCV7@2+1

2017GlobalPCVschedules3+1=232+1=573+0=59

POLICYEVIDENCE

Data:

Licensed2000:3+1

AssessmentofpostboosterantibodyresponsesinUKinfantsgivenareducedprimingscheduleof

meningococcalserogroupBandPCV13DavidGoldblatt1*,JoSouthern2*,NickJAndrews3,PollyBurbidge1,JoPartington4,LucyRoalfe1, Marta

ValentePinto4,VasilliThalasselis1,EmmaPlested4,HayleyRichardson1,MatthewDSnape4,ElizabethMiller1.

Funding

NIHRPolicyResearchProgramme[Grantnumber039/0031]NationalVaccineEvaluationConsortiumPILizMiller

BillandMelindaGatesFoundation[OPP1126431]:PIDavidGoldblatt

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Group V12m

V23m

V34m

V45m

V512m

V613m

V718m

1

(n=100)

2+1

DTaP/IPV/Hib

MenB

PCV13

Rota

DTaP/IPV/Hib

Rota

DTaP/IPV/Hib

MenB

PCV13

Rota

MenC/Hib

MenB

PCV13MMR

2

(n=100)

1+1

DTaP/IPV/Hib

MenB

Rota

DTaP/IPV/Hib

PCV13

Rota

DTaP/IPV/Hib

MenB

RotaSamples BloodA NPSwab A BloodB NP SwabB

213

106 97 103 91

107 102 100 86

2+1

1+1

CONSORT:

IgGGMCspostprimaryandvaccination

GoldblattetalLancetID,2017

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IgGProportionsaboveProtectiveTiter

GoldblattetalLancetID,2017

OPAActivity

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LancetInfectiousDiseaseOnline22rd November2017

Presentation title - edit in Header and Footer

Minutes of the 4th October 2017Meeting publishedToday

Minutes of the 4th October 2017:Decision to move to a 1+1 PCV schedule (3 m and 12m) based on date from PHE on current England and Wales IPD Epidemiology, Vaccine Type carriage prevalence and modelling as well as the recent 1+1 trial

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19

GLOBAL PCV INTRODUCTION STATUS - 2016

Gavi GlobalNational Introductions(asofDec2016)

57(78%) 139(72%)

SurvivingInfants haveaccesstoPCV

41M (51%) 69M(52%)

Surviving InfantsimmunizedwithPCV

29M(35%) 53M(37%)

Top10PCVcountrieswithmostunimmunized/underimmunized infants

Nigeria,Pakistan,Bangladesh,DRC,Uganda,Ethiopia,

Angola,Nepal,Kenya,Afghanistan

Philippines, Venezuela,Poland,SouthAfrica,

U.S.,DominicanRepublic,Brazil,Spain,Mexico,Argentina

(130)

IVAC VIEW-Hub and Gavi

© Bill & Melinda Gates Foundation |

GSK$540 million

Pfizer Inc.$555 million

$485 million tooverall $1.5 billion AMC

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PCV IS LARGEST SINGLE “SPEND” FOR GAVI

2000-202020% of $20.8 billion

UK: $2.462 billion

BhutanHondurasMongoliaSri LankaUkraine

Angola Armenia Azerbaijan BoliviaCongo Rep. Cuba Georgia GuyanaIndonesia. Kiribati. Moldova NicaraguaPNG. Timor Leste Uzbekistan Vietnam Ghana Nigeria Solomon Islands

$1045 $1580

Mean GNI Per capita over previous 3 years

Contribution$0.20/dose

Contribution15% pa increase

Inc to 100%Over 5 yrs

$3.05/dose

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BMGF SPONSORED ALTERNATE PCV DOSING STUDIES

South Africa (PI: Shabir Madhi)• Individual randomization• PCV10 and PCV13• 2+1 vs. 1+1 (6 or 14 wks +9mo)• Endpoints: immunogenicity, NPC• Results: 2Q2019

United Kingdom • Individual randomization• PCV13• 2+1 vs. 1+1 (2mo + 12 mo)• Endpoints: immunogenicity, NPC• Results: Nov 2017

India (PI: Ashish Bavdekar)• Individual randomization• PCV10 and PCV13• 3+0 and 2+1 vs. 1+1 (6 +9mo)• Endpoints: Immunogenicity, NPC• Results: May 2019

Vietnam (PI: Kim Mulholland)• Individual randomization• PCV10 and PCV13• 3+1, 3+0, 2+1,1+1, 0+1• Endpoints: Immunogenicity, NPC• Results: 4Q2019

Vietnam (PI: Lay-Myint Yoshida)• Cluster randomized• PCV10: 3+0, 2+1,1+1, 0+1• Endpoints: NPC, pneumonia• Results: 1Q2021

© Bill & Melinda Gates Foundation | 23

Gambia (PI: Grant Mackensie)• Cluster randomized• PCV13• 3+0 vs. 1+1 (6wks +9 mo)• Endpoints: NPC• Results: 2022

Eligibility criteria for transitioning to a 1+1• Mature PCV programme• High Coverage• Demonstrable Control of Vaccine Type Disease

NOT for PCV introduction

UK Experience will be crucial for the Global Effort

High Quality ongoing Surveillance Essential in the UKHigh Risk Groups may need Direct protection

In future a 0+1 could be considered

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Summary• Immunogenicityofa1+1scheduleisequivalenttoorsuperiortoa2+1schedulefor9ofthe13serotypesinPCV13

• InsettingswherevaccinetypeIPDiscurrentlyatverylowlevelsandcoverageoftheboosterishigh,primingwithasingledoseofPCV13mayhavelittleeffectonratesofpneumococcalinfection

• TheJCVIsdecisiontomovetoa1+1PCVscheduleintheUKgivesusanopportunitytoevaluatetheefficacyofa1+1scheduleinaHIC

• OngoingstudiesinLMICsofa1+1schedulewillhelpusunderstandwhetherthisapproachisuniversallyacceptable.

ACKNOWLEDGEMENTS• Liz Miller• Nick Andrews• Jo Southern

• Mary Ramsay• Shamez Ladhani

• University of Oxford: Trial Sponsorship• Matthew Snape and the OVG for recruitment to the 1+1 trial

Funding

NIHRPolicyResearchProgramme[Grantnumber039/0031]NationalVaccineEvaluationConsortium

BillandMelindaGatesFoundation[OPP1126431]: