Infectious Diseases Group Current Research

Project One: Tuberculosis (Tb) Vaccine Development

The currently available vaccine against Tuberculosis, BCG, has been given to more than three billion people worldwide, yet it fails to consistently provide protection against the bacterium that causes the disease. In 2007 we looked at potential reasons for why the BCG vaccine fails, since these will need to be taken into account when designing new more effective Tb vaccines.

We have discovered that parasite infection impairs the ability of BCG to protect against Tb, a finding that is supported by the observation that countries in which BCG is least effective also have high parasitic worm burdens. We are investigating which aspects of the protective immune response are affected by worm infection. We have shown that regulatory T cells can suppress BCG-induced immune responses. While in otherwise healthy individuals this does not affect protection against Tb, in worm-infected individuals the regulatory T cells may affect protection.

Efforts to develop a new, more effective vaccine for Tb have been hampered by a lack of understanding of what constitutes a protective memory immune response. We are currently trying to understand which CD4+ T cell subsets are important for mediating vaccine-induced protection against Tb. This information will be essential for the development of an effective vaccine.

Project Two: Multicentre Rotavirus Strain Surveillance

Rotavirus is a highly contagious virus that most commonly affects children under the age of two. It causes diarrhoea and vomiting, resulting in approximately 1000 hospitalisations in this country each year. In 2005 the Infectious Diseases Group established a multi-centre rotavirus strain surveillance study to monitor New Zealand's rotavirus strains pre- and post-introduction of a commercial rotavirus vaccine. This information will be vital for predicting the potential effectiveness of the vaccines that will be introduced into New Zealand.

Early indications from this study are that the rotavirus strains prevalent in the South Island each winter differ to those prevalent in the North Island. Furthermore, while the predominant strain seen globally and in NZ is consistently G1, the strains making up the remaining 40-50 % change quite dramatically each season and no-one knows why. Data collection for this study will be completed in 2008.

A rotavirus vaccine has been recommended for inclusion in the national immunisation schedule but has yet to be approved. If the vaccine is approved, we will aim to re-establish strain surveillance to determine the effect of the introduced vaccine on circulating rotavirus strains.

Project Three: Paediatric Respiratory Viruses in New Zealand

We have led a prospective epidemiological study assessing the risk factors for RSV hospitalisation and disease severity in Wellington during the winter months of 2003-2005. This study, which revealed that Maori and Pacific infants have a higher risk of being hospitalised from RSV bronchiolitis than NZ European infants, has now come to a close and the results published in the international journal Epidemiology & Infection.

In 2008 we will initiate a collaborative pilot study with the Wellington Asthma Research Group to identify possible interventions to RSV-induced hospitalisation. This study will initially focus on determining whether vitamin D levels, which have been shown previously to play a role in respiratory health, correlate with the ability to protect against RSV infection and hence disease severity.

Over recent years bronchiolitis hospitalisation rates have been increasing in NZ. In 2007 we were the first to show that the recently discovered virus, human bocavirus, which is thought to cause severe respiratory illness in young children, is present in this country. Collectively this information is vital for understanding why NZ has such high hospitalisation rates for children with respiratory disease.

Clinical Relevance and Future Direction

Preventing infectious disease through vaccination is the ultimate aim of the research conducted by the Infectious Diseases Group. Currently we do not have effective vaccines in New Zealand against any of the pathogens described above, nor are we assured that future vaccines created internationally will work in our unique environment.

In the future it is hoped that we will be able to identify a correlate of immune protection to expedite Tb vaccine development and testing. Without such a correlate it will take years to test each vaccine, making it even longer before we can effectively protect the New Zealand population against Tb infection.

We also hope to have identified the factors that contribute to our high RSV hospitalisation rates so that we can start looking at possible interventions to reduce the incidence of severe RSV infection in New Zealand .

Although the rotavirus vaccine is now used in many other developed countries it has yet to be approved for New Zealand and this could take years. Studies such as ours will determine whether the vaccine is likely to protect New Zealand infants against rotavirus infection.

Collaborators

Assoc Prof Glenn Buchan, Department of Microbiology and Immunology, University of Otago, New Zealand
Drs Bryce Buddle, Geoff deLisle and Michel Denis, AgResearch, Wallaceville, New Zealand
Dr Carlos Camargo, Massachusetts General Hospital, Boston, USA
Dr Catherine Cohet, Dodet Bioscience, Lyon, France
Prof Julian Crane and Dr Tristram Ingham, Clinical Epidemiology, Wellington School of Medicine, University of Otago, New Zealand
Prof Chris Cunningham, Research Centre for Maori Health and Development, Massey University, New Zealand
Prof Brett Delahunt, Department of Pathology, Wellington School of Medicine, University of Otago, New Zealand
Prof Keith Grimwood, Department of Paediatrics and Child Health, Wellington School of Medicine, University of Otago, New Zealand
Dr Ronan O'Toole, School of Biological Sciences, Victoria University of Wellington, New Zealand
Prof Neil Pearce, Centre for Public Health Research, Massey University, New Zealand

Also New Zealand contributions by:
Aotea Pathology
Capital & Coast Health Laboratory
Health Waikato
Hutt Hospital Laboratory
Medlab South
Paediatric units and laboratories at Canterbury Health
Starship Auckland Hospital
Southern Community Laboratories