Preventing Burkholderia bacterial infections using novel vaccine technologies

Project Duration – 1 years

Dr Nick Scott from the University of Melbourne and the Doherty Institute is using bacteria’s own tricks against it to research and develop a new way to produce vaccines which may protect people from Burkholderia lung infections.

People with cystic fibrosis are susceptible to a range of infections with Burkholderia bacteria, which decreases their life expectancy and excludes them from lifesaving tissue transplants.

With Cure4CF funding, Dr Scott’s team will:

1. Establish a novel method to create proteins known as glycoproteins using cutting edge “glycoengineering” approaches.
2. Test the production of novel glycoprotein vaccines against Burkholderia bacteria.

The team have already shown that glycoproteins can be produced using glycoengineering in bacterial systems.  They have also shown that these proteins are potently recognised by the immune system making them ideally suited for use as vaccines. By teaching our bodies to recognise these glycoproteins, we can develop immunity without being exposed to the bacteria itself.

The problem with Burkholderia bacteria

The Burkholderia genus of bacteria are usually found in soil and water and cause infection in people with cystic fibrosis (CF). Burkholderia species such as Burkholderia cenocepacia are a significant concern due to their poor long-term prognosis; their patient-to-patient transmissibility; and their resistance to antibiotics. In Australia alone, more than 50 people were identified with Burkholderia cepacia in 2021 (CF in Australia report 2021). Infections with Burkholderia species are associated with high mortality rates. Burkholderia cenocepacia-positive CF patients are excluded from lifesaving tissue transplants due to the risk associated with post-transplant infections.

Why vaccination?

By developing new systems to produce vaccines Dr Scott’s team hopes to reduce the rate of Burkholderia infection in CF patients. By using glycoengineering to produce prototype vaccines the team hopes to establish a scalable and inexpensive way to make Burkholderia focused vaccines. If successful, this system will allow the production of these vaccines cheaply and easily hopefully leading to a dramatic saving in health care costs by limiting Burkholderia infections.

Dr Scott hopes to develop the first glycosylation-focussed vaccine for Burkholderia infections.

The research may also lead to new treatments for people whose lungs are already infected with Burkholderia.

What type of vaccine?

The project will establish and prototype the production of Burkholderia glycoproteins using the common laboratory bacteria Escherichia coli.

In the age of COVID-19 we became familiar with different types of vaccines, especially the mRNA vaccines used against COVID-19. There are many other types of vaccines used to prevent disease. Some other types include live attenuated vaccines such as the measles mumps rubella (MMR) vaccine. This is where the whole microorganism is made relatively harmless and then delivered to people to create an immune response to protect us from the real infection.

Dr Scott will instead use a conjugate vaccine, where only part of the organism is used, in this case the sugar molecules from the surface of the bacteria. Often these bacterial sugar molecules are part of the disguise bacteria use to avoid human detection. By joining (or ‘conjugating’) a harmless protein to these bacterial sugar molecules, the immune system senses both the protein and the bacterial sugar molecules. In this way scientists use conjugation to help our immune system to recognise the bacteria, respond and provide protection.

Glycoconjugate vaccines (joining proteins to sugar molecules) are some of the safest and most widely used vaccines in human health. They have been used in vaccination against typhoid, pneumonia, and meningitis.

The team have shown that during Burkholderia infections these complexes are recognised and targeted by our immune response. The team will use glycoengineering to prepare vaccines which can help our bodies produce an immune response so that on exposure to the bacteria, it can be eradicated.

What will be the pathway to moving this therapy into the clinic?

The goal of this application is to establish a new platform for the creation of vaccines that can protect individuals with CF against Burkholderia infections. If successful, the Scott lab will seek to use this seed funding to generate preliminary data for an Australian Research Council linkage application with industrial partners.

About Dr Scott

Dr Scott received his PhD from the University of Sydney in 2012 on developing approaches to study bacterial glycosylation. During his postdoctoral training in Canada Dr Scott developed quantitative proteomics tools to identify bacterial glycosylation events across a range of pathogens revealing bacterial glycosylation to be far more widespread than once thought. In 2016 Dr Scott returned to Australia and in 2017 established his independent research group in the Department of Microbiology and Immunology at the University of Melbourne.

Within the Scott lab, his team seeks to better understand bacterial glycosylation systems with the goal to harness microbial glycosylation systems to improve human health, both as therapeutic targets and as glycoengineering tools. Working closely with microbial glycosylation labs from around the world Dr Scott’s work has demonstrated that bacterial glycosylation is an exciting alternative platform to produce recombinant glycoproteins making these systems ideal to produce next-generation vaccines.

In 2019 in recognition of his contribution to the field of glycoconjugate research Dr Scott was awarded the IGO Young Glycoscientist Award from the International Glycoconjugate Organization and in 2020 Dr Scott was awarded an ARC Future Fellowship. Most recently, in 2021 Dr Scott was awarded the prestigious Frank Fenner Award from the ASM (in recognition of his contributions to the field of microbial glycosylation) as well as was named one of the 40 under 40 Rising Stars in proteomics and metabolomics by the Journal of Proteome Research.