Optimising pneumococcal conjugate vaccine schedules https://www.meningitis.org/mrf-conference-2017

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Optimising Pneumococcal Conjugate Schedules
Professor David Goldblatt
UCL Great Ormond Street Institute of Child Health
and
Great Ormond Street Hospital for Children NHS Foundation Trust
§ Vaccine Schedule Refinement in the UK 1990-2015
§ PCV introduction and disease control
§ Possible approaches to optimising PCV use
§ Results of a PCV 2+1 vs 1+1 Randomised Control Trial
§ Global PCV considerations

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1990 2000 2010 2015 202099 06 13
Men C
3+0
Men C
2+1
Men C
1+1
+ adol
Men C
0+1
Men ACWY
adol
Men B
2+1
Hib
3+0
Hib
3+1
Hib
Booster
campaign
Licensed
3+1
PCV7
2+1
PCV13
2+1
Licensed
3+1
HPV
3 dose
HPV
2 dose
08 14
UK Vaccine
Introduction
and Schedule
Changes
YEAR 2000 2006/7 2010/11 2013/14
UK (2+1)
USA (3+1)
PCV7 IPD < 2y 99% reduction1
PCV7 Carriage
Near Elimination2
PCV7 IPD all ages
86% reduced1
13-7
69%2
PCV13-7 IPD <2
89% Reduction1
PCV7 IPD < 5y
97%3
PCV7 Carriage Mass.
Children near elimination4
PCV13-7 IPD < 5
93%5
1 Waight et al 2015, 2 van Hoek et al 2014, 3 Feikin et al 2013, 4 Wroe et al 2012, 5 Moore et al 2015, 6 Yildrim et al 2017
PCV13-7 Carr
Mass. Children
Very Low6
Impact of
PCV
Introduction

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Invasive pneumococcal disease
incidence rate per 100,000
popn by age grouping, 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 10-14
years
15-44
years
45-64
years
65-74
years
75-79
years
80+ years
Age range
Rateper100,000
population
1996/97 1997/98
1998/99 1999/00
2000/01 2001/02
2002/03 2003/04
2004/05
Data courtesy of the Health Protection Agency
Optimising the use of
Pneumococcal Conjugate Vaccines
PCV7 Type IPD
0.32/100,00035.78/100,000
17.73/100,000
0.55/100,000
• Australian paper
2017
3+0 2+1

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Invasive pneumococcal disease
incidence rate per 100,000
popn by age grouping, 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 10-14
years
15-44
years
45-64
years
65-74
years
75-79
years
80+ years
Age range
Rateper100,000
population
1996/97 1997/98
1998/99 1999/00
2000/01 2001/02
2002/03 2003/04
2004/05
Data courtesy of the Health Protection Agency
Optimising the use of
Pneumococcal Conjugate Vaccines
PCV7 Type IPD
0.32/100,000
35.78/100,000
17.73/100,000
0.55/100,000
Risks of removing this dose?
Whitney et al. Lancet 2006;368:1495-502

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Andrews NJ et al. Lancet Infect Dis 2014;14:839-46
1dose 2.5<13m VE 38% (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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JCVI 2006: PCV7 @ 2+1
2017 Global
PCV schedules
3+1 = 23
2+1 = 57
3+0 = 59
POLICYEVIDENCE
Data:
Licensed 2000: 3+1
Assessment of post booster antibody responses in
UK infants given a reduced priming schedule of
meningococcal serogroup B and PCV13
David Goldblatt1*, Jo Southern2*, Nick J Andrews3, Polly Burbidge1, Jo Partington4, Lucy Roalfe1, Marta
Valente Pinto4, Vasilli Thalasselis1, Emma Plested4, Hayley Richardson1, Matthew D Snape4, Elizabeth Miller1.
Funding
NIHR Policy Research Programme [Grant number 039/0031]
National Vaccine Evaluation Consortium
PI Liz Miller
Bill and Melinda Gates Foundation [OPP1126431]:
PI David Goldblatt

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Group V1
2m
V2
3m
V3
4m
V4
5m
V5
12m
V6
13m
V7
18m
1
(n=100)
2+1
DTaP/IPV/
Hib
Men B
PCV13
Rota
DTaP/IPV/
Hib
Rota
DTaP/IPV/
Hib
Men B
PCV13
Rota
MenC/Hib
Men B
PCV13
MMR
2
(n=100)
1+1
DTaP/IPV/
Hib
Men B
Rota
DTaP/IPV/
Hib
PCV13
Rota
DTaP/IPV/
Hib
Men B
Rota
Samples Blood A NP Swab A Blood B NP Swab B
213
106 97 103 91
107 102 100 86
2+1
1+1
CONSORT:
IgG GMCs post primary and vaccination
Goldblatt et al Lancet ID, 2017

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IgG Proportions above Protective Titer
Goldblatt et al Lancet ID, 2017
OPA
Activity

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Lancet Infectious Disease
Online 22rd November 2017
Presentation title - edit in Header and Footer
Minutes of the
4th October 2017
Meeting published
Today
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 Global
National Introductions (as of Dec 2016)
57 (78%) 139 (72%)
Surviving Infants have access to PCV
41M (51%) 69M (52%)
Surviving Infants immunized with PCV
29M (35%) 53M (37%)
Top 10 PCV countries with most
unimmunized/underimmunized infants
Nigeria, Pakistan,
Bangladesh, DRC,
Uganda, Ethiopia,
Angola, Nepal, Kenya,
Afghanistan
Philippines, Venezuela,
Poland, South Africa,
U.S., Dominican
Republic, Brazil, Spain,
Mexico, Argentina
(130)
IVAC VIEW-Hub and Gavi
© Bill & Melinda Gates Foundation |
GSK
$540 million
Pfizer Inc.
$555 million
$485 million to
overall $1.5 billion AMC

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PCV IS LARGEST SINGLE “SPEND” FOR GAVI
2000-2020
20% of $20.8 billion
UK: $2.462 billion
Bhutan
Honduras
Mongolia
Sri Lanka
Ukraine
Angola Armenia Azerbaijan Bolivia
Congo Rep. Cuba Georgia Guyana
Indonesia. Kiribati. Moldova Nicaragua
PNG. Timor Leste Uzbekistan Vietnam
Ghana Nigeria Solomon Islands
$1045 $1580
Mean GNI Per capita over previous 3 years
Contribution
$0.20/dose
Contribution
15% 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 UK
High Risk Groups may need Direct protection
In future a 0+1 could be considered

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Summary
• Immunogenicity of a 1+1 schedule is equivalent to or
superior to a 2+1 schedule for 9 of the 13 serotypes in
PCV13
• In settings where vaccine type IPD is currently at very low
levels and coverage of the booster is high, priming with a
single dose of PCV13 may have little effect on rates of
pneumococcal infection
• The JCVIs decision to move to a 1+1 PCV schedule in the
UK gives us an opportunity to evaluate the efficacy of a
1+1 schedule in a HIC
• Ongoing studies in LMICs of a 1+1 schedule will help us
understand whether this approach is universally
acceptable.
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
NIHR Policy Research Programme [Grant number 039/0031]
National Vaccine Evaluation Consortium
Bill and Melinda Gates Foundation [OPP1126431]: