Pneumococcal Research

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The Pneumococcal Research Group, led by Professor Kim Mulholland, works across three distinct but closely-related sub-groups to develop, evaluate and enhance vaccination strategies worldwide:

  • Clinical and Epidemiology
  • Microbiology
  • Immunology

The group is currently conducting a vaccine clinical trial in Ho Chi Minh City, whole cell vaccine studies in Bandung and vaccine impact studies in Mongolia, Lao PDR, and Papua New Guinea. In Fiji the group is conducting a program of work evaluating the introduction of Pneumococcal, Rotavirus and Human papillomavirus vaccines.

In 2012 the group was awarded a Centre of Excellence grant from the National Health and Medical Research Council (NHMRC).

The pneumococcal research program covers four main areas:

Serotype replacement
The only way to study pneumococcal population biology, and the impact of vaccines on it, is to study nasopharyngeal carriage of pneumococci.  It is known that children frequently carry two or more serotypes, and that density of carriage is important for the likelihood of disease and transmission.  Yet all major studies have relied on simple microbiology, sampling only a few pneumococcal colonies from the agar plate.  In 2006, Murdoch Children's secured a small sub-grant from the Helsinki-based PneumoCarr mathematical modelling consortium to address this.  With support from the Bill and Melinda Gates Foundation this grew to be a global program (PneuCarriage project), led by Dr Catherine Satzke, which brought together field sites from Asia and Africa, along with 15 leading pneumococcal research groups around the world.  This has established the most appropriate methodology that is now being used in major field sites.

Schedules
With the support of the Australian National Health and Medical Research Council (NHMRC), the team has established a major research program in Ho Chi Minh City, in partnership with Menzies School of Health Research and the Pasteur Institute.  The main trial, which compares various schedules of Pneumococcal Conjugate Vaccines (PCV10 and PCV13) with co-administered Infanrix-Hexa, uses the full range of pneumococcal immunological tests, along with a novel new B-cell assay developed in Fiji, and the microbiology technology developed as part of the PneuCarriage project, to evaluate the vaccines and schedules.  Already the most detailed and comprehensive pneumococcal vaccine trial, it is now being developed further and extended, with a grant from the Bill and Melinda Gates Foundation.  

Vaccine Impact in Asia
There are two components to this issue: the burden of pneumonia in Asia, and the contribution of pneumococcus to that burden.  To contribute to the first component we are undertaking, in partnership with Menzies School of Health Research in Darwin and the Pasteur Institute of Ho Chi Minh City, a study of the pneumonia burden in Ho Chi Minh City.  Vaccine impact is the only way to accurately determine how much of the pneumonia burden is vaccine preventable.  We are currently leading studies in Fiji, Laos and Mongolia to evaluate the impact of pneumococcal vaccine introduction on pneumonia incidence and pneumococcal carriage. Most countries are unable to show evidence of vaccine impact. The Bill and Melinda Gates Foundation is funding a study to demonstrate how carriage surveillance in children with pneumonia can be used to estimate the pneumococcal conjugate vaccine coverage required to show evidence of herd immunity, and monitor the vaccine’s impact on carriage, and thereby provide information for national planners to maximize the effectiveness of their immunization programs. This is led by Associate Professor Fiona Russell.

New pneumococcal vaccines
The leading non-capsular pneumococcal vaccine under development is a non-encapsulated whole cell vaccine developed in Boston.  With support from the Bill and Melinda Gates Foundation, Program for Appropriate Technology in Health (PATH) is now developing this vaccine, which will be produced in Indonesia by the Biofarma Indonesia company.  MCRI is currently leading preparatory studies in collaboration with Professor Cissy Kartasasmita at Universitas Padjadjaran (UNPAD) in Bandung, Indonesia and we will lead the forthcoming trials in Bandung and Lombok.

Group Leaders: 
Group Members: 
Anne Balloch
Role: 
Research Fellow - Immunology
Dr Nick Fancourt
Role: 
Research Fellow
Dr Sam Manna
Role: 
Research Officer - Microbiology
Dr Cattram Nguyen
Role: 
Biostatistician (Research Fellow)
Dr Claire Von Mollendorf
Role: 
Senior Research Officer
Dr Lien Anh Ha Do
Role: 
Research Officer - Virology
Eleanor Neal
Role: 
Research Assistant and PhD Candidate
Belinda Ortika
Role: 
Research Assistant - Microbiology
Casey Pell
Role: 
Research Assistant - Microbiology
Ahmed Alamrousi
Role: 
Research Assistant - Microbiology
Monica Nation
Role: 
Research Assistant - Microbiology
Rachel Marimla
Role: 
Research Assistant - Immunology
Jordan Nathanielsz
Role: 
Research Assistant
Dr Jocelyn Chan
Role: 
PhD student
Dr Ruth Lim
Role: 
Master's Student
Helen Thomson
Role: 
Research Manager
Kathryn Bright
Role: 
Clinical Coordinator - based in Vietnam
Dr Anushi Rajapaksa
Role: 
Senior Research Officer
Jana Lai
Role: 
Research Officer - based in Lao PDR
Beth Temple
Role: 
Program Manager - Vietnam Project
Jayne Manning
Role: 
PhD Student - Microbiology
Ryan Toh
Role: 
PhD Student - Immunology
Laura Boelsen
Role: 
PhD Student - Microbiology
Lucy Crouch
Role: 
Personal Assistant

Current Projects are listed below.  All projects involve a combination of team members from clinical epidemiology, microbiology and immunology:

Pneumococcal Vaccine Research and Development

A. Vietnam reduced dose pneumococcal clinical trial

Led by Professor Mulholland and funded by the Australian National Health and Medical Research Council.  The trial is designed to answer the remaining questions needed to implement a 2+1 schedule on a global scale. These include:

  • Evaluation of the immunogenicity of the two new-generation conjugate vaccines (PCV10 and PCV13) in a 2+1 schedule, in comparison with existing recommended schedules;
  • Evaluation of the impact on carriage of the two new-generation conjugate vaccines (PCV10 and PCV13) in a 2+1 schedule, in comparison with existing recommended schedules and an unvaccinated control group;
  • The immunogenicity of co-administered Hib containing combination vaccines in a 2+1 schedule;
  • Evaluation of the immunogenicity and impact on carriage of PCV10 in an experimental 1+1 schedule (2 and 6 months).

Vietnam study extension funded by Bill and Melinda Gates Foundation
The add-on study proposes to fully evaluate the 0+1 and 1+1 schedules for both the existing PCVs and to extend the length of follow up of the existing trial to strengthen its power to address the key questions.

B. Mongolia pneumococcal vaccine impact evaluation
Principal Investigator Professor Mulholland in collaboration with WHO and Mongolia Ministry of Health. Funded by the GAVI Alliance. The primary objective is to evaluate the impact of PCV introduction on the incidence of radiological pneumonia among under-5 children in four large districts of Ulaanbaatar.

Blog post: Fighting a forgotten killer in the land of Chinggis Khan

C. Nasopharyngeal carriage surveillance (PneuCAPTIVE Project)
Principal Investigator Associate Professor Fiona Russell. Collaborating with WHO Western Pacific Regional Office, Lao Ministry of Health, Lao-Oxford- Mahosot Hospital-Wellcome Trust-Research Unit (LOMWRU), the University of Western Australia, the Institute of Medical Research, PNG and Mongolia Ministry of Health, and St George’s Hospital, UK. This project aims to estimate the PCV coverage required to show direct and indirect immunity, by using innovative methods suitable for low- and middle-income countries.

D. Lao PDR pneumococcal vaccine impact evaluation
This project, funded by the GAVI Alliance, is co-led by Associate Professor Fiona Russell and Professor Kim Mulholland in collaboration with the World Health Organization (WHO) and the Lao Ministry of Health, and will provide information on the impact of the newly introduced pneumococcal conjugate vaccine on childhood pneumonia and carriage. The study’s design was presented by A/Prof Russell at the WHO Expert consultation on PCV Impact Evaluation meeting, Geneva, in 2013

E. Fiji new vaccine evaluation project
This project is a collaboration between Murdoch Children's and the Fiji Ministry of Health. It is co-led by Associate Professor Fiona Russell and Professor Kim Mulholland, and funded by Australian Aid. The NVEP aims to improve surveillance at the Fiji government’s public health laboratory and evaluate the impact of pneumococcal conjugate vaccine, rotavirus vaccine, and human papillomavirus vaccines which the government recently introduced. The team will evaluate the pneumococcal conjugate vaccine’s impact on carriage and disease, and we are transferring technology from MCRI to the Fiji Ministry of Health to support meningitis surveillance. The NVEP is measuring the impact of rotavirus vaccine on diarrhoea in Fiji; monitoring for intussusception; and providing support for surveillance. In addition, the NVEP is evaluating reduced dose HPV schedules, and will establish surveillance for human papillomavirus infection in Fiji. 

F. Typhoid project (Fiji)
Assessment project funded by Australian Aid and led by Prof Mulholland. While typhoid has long been recognized as a problem for Fiji and other Pacific nations, that dramatic increase in cases since 2007 has now placed Fiji in the highest category of typhoid endemic countries, along with countries like Nepal and Pakistan.  The reasons for this are unknown. 
Following the perceived failure of a vaccination program initiated by WHO and CDC in 2010, the Fijian Ministry of Health requested Murdoch Children's to help them to find a solution.  In 2012, the Institute convened a meeting of leading typhoid specialists in Fiji to address the issue.  The paradoxes of typhoid in Fiji and the lack of objective epidemiological, clinical and microbiological information were highlighted in the meeting. 
This led to an AusAID (now Australian Aid) funded project to implement the recommendations of the meeting and get to the bottom of the problem. Murdoch Children's is now leading a project in collaboration with Melbourne University (Prof Strugnell), University of Otago (Prof Crump), Oxford University Vietnam (Dr Baker) and the Sanger Institute UK (Prof Dougan) to address this.

G. Modelling the effect of social contact (Fiji)
Associate Professor Fiona Russell is the Prinicipal Investiagtro on this Bill and Melinda Gates Foundation funded project in Fiji. The project aims to show whether the frequency and intensity of social contact effects pneumococcal carriage rates and density, and if so, whether PCV10 is able to overcome the effects of social contact on the carriage of PCV10 serotypes. This study will contribute to the understanding of why there are ethnic and regional pneumococcal disease burden differences and help to elucidate whether the perceived lower pneumococcal disease burden in India, and more broadly in Asia, in comparison with Africa, may be partly explained by the effect social behaviour has on pneumococcal carriage. 

H. Bandung Pneumococcal Project
Pneumococcal carriage in Indonesian infants ahead of the Streptococcus pneumoniae whole cell vaccine efficacy trial. Principal Investigator Prof Mulholland, in collaboration with Universitas Padjadjaran. Funded by PATH.

Currently, the only pneumococcal vaccines licenced for use in children are pneumococcal conjugate vaccines (PCVs). Although PCVs are successful at reducing pneumococcal disease overall, they are expensive to produce and they only protect against a subset of pneumococcal serotypes, so their use can lead to increased carriage and disease caused by non-vaccine serotypes (serotype replacement).

S. pneumoniae whole cell vaccine (PATH-wSP) has been developed as a low-cost alternative to pneumococcal conjugate vaccines (PCVs), which could deliver broad protection against the pneumococcus. PATH-wSP has undergone safety testing (Phase I clinical trials) in healthy adults, and the first clinical trials in children are planned to take place in Kenya and Indonesia.

Indonesia is the world’s fourth most populous country and there are no plans to introduce PCVs to the Indonesian National Immunization Program.
In collaboration with Professor Cissy Kartasasmita of Universitas Padjadjaran (UNPAD) in Indonesia, we are leading a new research project to acquire baseline information on pneumococcal carriage that will help inform the design of (PATH-wSP) efficacy trials.

The research will also provide additional evidence that the pneumococcus is an important and common pathogen in Indonesian infants. Understanding nasopharyngeal carriage of the pneumococcus, in both urban and rural populations, will be essential for evaluating the vaccine’s true impact.
The baseline carriage study will have two components:

a longitudinal study to investigate pneumococcal carriage dynamics including serotype-specific acquisition and clearance in the first year of life, and
a cross-sectional study to generate pan-Indonesian data on the carriage rates of pneumococci and other important colonizing pathogens. 

I. PneuCarriage follow-up study
‘Monitoring pneumococcal carriage and vaccine impact’. Co-principal Investigators Dr Catherine Satzke and Prof Kim Mulholland. This project is funded by Bill and Melinda Gates Foundation to establish appropriate serotyping methods for the investigation of pneumococcal carriage in the context of measuring pneumococcal conjugate vaccine impact in low-income countries.

Centre of Research Excellence in Pneumococcal Vaccinology
Project led by Prof Mulholland and funded by National Health and Medical Research Council.

Funding: 
  • Australian Aid
  • Bill and Melinda Gates Foundation
  • GAVI Alliance
  • National Health and Medical Research Council
  • PATH
Collaborations: 
  • Centre for International Child Health, The University of Melbourne
  • Charles Darwin University
  • Edith Cowan University
  • Emory University, Atlanta, USA
  • John Hopkins University, Baltimore, USA
  • Lao PDR Ministry of Health
  • Laos Oxford Mahosot Wellcome Research Unit 
  • London School of Hygiene and Tropical Medicine
  • Medical Research Council (MRC)
  • Menzies School of Health Research
  • Ministry of Health, Fiji
  • Mongolian Ministry of Health
  • Otago University, Dunedin, NZ
  • Papua New Guinea Institute of Medical Research
  • Pasteur Institute, Vietnam
  • The Respiratory and Meningeal Pathogens Research Unit (RMPRU) /Wits, Johannesburg, South Africa
  • St George’s Hospital, London, UK
  • St George’s, University of London (SGUL), UK
  • Telethon Kids
  • Universitas Padjadjaran (UNPAD), Bandung, Indonesia
  • University of Idaho, Moscow, USA
  • University of Oxford, UK
  • University of Western Australia
  • University of Witswatersrand, Johannesburg, South Africa
  • World Health Organization (WHO), Western Pacific Regional Office
  • World Health Organization (WHO) HPV Reference Laboratory, The Women’s Hospital
  • World Health Organization (WHO) Rotavirus Regional Reference Laboratory, MCRI
  • Women’s Centre for Infectious Diseases, University of Melbourne