Murdoch Children’s Research Institute
Infection and Immunity
Trained as a paediatrician, I have spent most of my professional life working in low and middle income countries, with a particular focus on childhood pneumonia, both management and prevention by vaccination. The latter led me into a series of Hib vaccine trials in the Gambia in the early 90s, culminating in a large phase 3 trial of a Hib vaccine involving 42,000 infants with pneumonia as the co-primary outcome. Between 1995 and 2000 I was based at WHO, geneva where I had responsibilities covering research related to Integrated Management of Childhood Illness (IMCI) and vaccines for the prevention of pneumonia, both Hib and pneumococcal vaccines. I was involved in the design and/or oversight of all the major pneumococcal conjugate vaccine trials that were undertaken in low and middle income countries. In the years since leaving WHO I have been actively involved in pneumococcal vaccine research in Fiji, Australia, Vietnam and Mongolia. I also co-led the global Hib Initiative project that facilitated the introduction of Hib vaccines throughout the world between 2005 and 2010. I have served on the WHO SAGE Pneumococcal Vaccines Working Group, and I am currently a member of the WHO SAGE.

Moderator Of 1 Session

Session Type
Plenary Session
Date
Tue, 21.06.2022
Session Time
09:00 - 10:30
Room
Grand Ballroom East
Session Description
Please note: Each presentation is followed by 5 to 10 minutes of Q&A. The audience is encouraged to send questions to the speakers from the beginning of their presentations. Q&A time is included in each speaker’s presentation duration, accounting for at least 25% active learning for the maximum registrants anticipated.

Presenter Of 4 Presentations

Optimal PCV Schedules for Children in Low and Low Middle Income Countries: Evidence from Vietnam (ID 43)

Session Type
Plenary Session
Date
Tue, 21.06.2022
Session Time
09:00 - 10:30
Room
Grand Ballroom East
Lecture Time
09:00 - 09:30

O010 - A TRIAL OF REDUCED DOSE SCHEDULES OF PCV10 AND PCV13 IN HO CHI MINH CITY, VIETNAM (ID 370)

Session Type
Parallel Session
Date
Mon, 20.06.2022
Session Time
15:20 - 16:35
Room
Grand Ballroom West
Lecture Time
15:45 - 15:55

Abstract

Background

Use of pneumococcal conjugate vaccines (PCVs) in low and middle income countries has been limited by vaccine price. Reduced dose schedules could benefit many children.

Methods

In Ho Chi Minh City, Vietnam we enrolled 2501 infants in a trial comparing 1+1 (2&12m) and 0+1 (12m) schedules of PCV10 (Synflorix®) and PCV13 (Prevenar-13®; n=400 per group) with controls (n=900). Nasopharyngeal carriage and immunogenicity (by ELISA and OPA) were measured at selected timepoints up to 24 months of age.

Results

At 24m (primary endpoint), 1+1 schedules of PCV10 or PCV13 reduced the carriage of serotypes included in that vaccine (VT carriage) by 59% (95% CI 26-78) and 66% (42-80), respectively. At 18m, both reduced VT carriage by two-thirds. Immunologically, both offered some protection between doses (greater with PCV10 for 5/10 serotypes) and both generated a strong booster response (stronger with PCV13 for most serotypes). A 0+1 schedule of PCV10 or PCV13 also reduced VT carriage and elicited a good antibody response, albeit to a lesser extent than a 1+1 schedule.

Conclusions

1+1 PCV schedules at 2&12m provide protection against carriage to 24m, indicating that these schedules will be adequate to maintain herd immunity. This may be supported by a single dose at 12m for unvaccinated children.

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O013 - IMMUNOGENICITY 6-MONTHS POST-BOOSTER FOLLOWING MIXED PRIMARY AND BOOSTER DOSE SCHEDULES FROM THE PREVIX RANDOMISED CONTROLLED TRIALS OF 13- AND 10-VALENT PNEUMOCOCCAL CONJUGATE VACCINES. (ID 635)

Session Type
Parallel Session
Date
Mon, 20.06.2022
Session Time
15:20 - 16:35
Room
Grand Ballroom West
Lecture Time
16:15 - 16:25

Abstract

Background

The objective was to evaluate the immunological responses to pneumococcal conjugate vaccine (PCV) combination schedules from birth through the second year of life.

Methods

In PREVIX_BOOST, Aboriginal children previously enrolled PREVIX_COMBO, a 3-arm RCT of head-to-head standard or combined infant schedules of PCV13 (P) and/or PHiD-CV10 (S), were further randomised 1:1 to a booster dose of either +P or +S at 12-months of age. Geometric mean concentration (GMC) and proportion of children with IgG concentration above specified thresholds 6-months post-booster are reported according to _PPP+P vs _PPP+S, _SSS+P vs _SSS+S, and SSSP+P vs SSSP+P.

Results

From 03/2013 to 09/2018, 261 children were allocated to +P (n=131) or +S (n=130). Pneumococcal GMCs were generally low, although significantly higher in the +P group against 1, 3, 5, 6A, 6B, 9V, and 23F, higher in the +S group against 19F, and not different against 4, 7F, 14, 18C, and 19A. GMC comparisons stratified by primary schedules further revealed that i) if priming includes PCV13, either +P or +S can be used, ii) serotype 1 and 3 GMCs were below IPD threshold in the _SSS+S group, and iii) benefit of a 4-dose combined primary schedule was not sustained.

figure 1 - gmcs.png

Conclusions

All antibody responses rapidly waned 6-months post-booster, particularly in the _SSS+S group. If the infant schedule includes PCV13, either PCV13 or PHiD-CV10 can be used as a booster. However, as PCV13 at 2 months of age is not immunogenic, PHiD-CV10 should be the first infant dose. Combined schedules offer flexibility for customising PCVs.

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O066 - IMPACT OF PCV13 INTRODUCTION ON SEVERE LOWER RESPIRATORY TRACT INFECTIONS ASSOCIATED WITH RESPIRATORY SYNCYTIAL VIRUS OR INFLUENZA IN HOSPITALISED CHILDREN IN ULAANBAATAR, MONGOLIA (ID 869)

Session Type
Parallel Session
Date
Wed, 22.06.2022
Session Time
15:05 - 16:50
Room
Grand Ballroom Centre
Lecture Time
17:31 - 17:39

Abstract

Background

PCV13 was introduced in Mongolia in a phased manner, from June 2016. We aimed to evaluate the impact of PCV13 introduction on the incidence of severe lower respiratory tract infections (LRTIs) and those associated with RSV or influenza among hospitalised children <2 years in 4 districts of Ulaanbaatar (SK:Songinokhairkhan, SB:Sukhbataar, BZ:Bayanzurkh and CHD:Chingeltei) for the period April 2015-March 2020.

Methods

This study is nested in a pneumonia surveillance project which enrolled hospitalised children aged 2-59 months who met an adapted WHO pneumonia case definition. We included children <2 years with arterial O2 saturation<93%, and children with radiological confirmed pneumonia. We tested nasopharyngeal swabs for RSV and influenza using qRT-PCR. Incidence rate ratios (IRR) comparing pre- and post-vaccine periods were estimated using negative binomial models with PCV13 introduction, district and time, as covariates.

Results

In total 5,680 children were enrolled; 1,977 (34.8%) and 360 (6.3%) were positive for RSV and influenza, respectively. The RSV and influenza peaks coincided with the peak of LRTIs cases from the surveillance project (Figure 1). No significant reductions in incidences of LRTIs [IRR 0.97 (95% confidence interval (CI) 0.78-1.21)], nor LRTIs associated with RSV [IRR 0.90 (95%CI 0.64-1.25)] or influenza [IRR 0.87 (95%CI 0.52-1.46)] were observed after PCV introduction.

Figure 1-LRTIs and LRTIs associated with RSV and influenza cases

figure 1-abstract isppd 2022.png

Conclusions

PCV13 introduction does not have a clear impact on reducing the incidence of all LRTIs as well as LRTIs associated with RSV or with influenza. Separate models exploring impact by district for different endpoints will also be presented.

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