Taking the next steps in preventing Burkholderia bacterial infections: developing new antibodies for a vaccine

Project Duration – 1 Year

In 2023, Cure4CF funded an exciting Burkholderia bacteria vaccine project with Associate Professor Nick Scott from the University of Melbourne. In 2025, we are excited to support the project’s next stage.

Associate Professor Nick Scott is teaming up with Professor Ethan Goddard-Borger to advance work to exploit bacterial surface carbohydrates and produce vaccines which could both protect people from Burkholderia Cenocepacia lung infections and provide a treatment for those who already have a Burkholderia infection.

During 2023, the team established a method to create the key ingredients of the vaccine, bacterial surface carbohydrates attached to proteins and tested these in the laboratory. Building on this work, the current project aims to use these proteins to develop Burkholderia-specific antibodies. By using these new vaccines to create antibodies, this research seeks to provide a new way to both protect at risk individuals as well as combat established Burkholderia infections.

With Cure4CF funding, Dr Scott’s team will:

1. Produce a group of the glycoproteins and raise monoclonal antibodies which are needed to generate a vaccine
2. Assess the ability of the antibodies to bind to bacteria and enable them to be engulfed by immune cells.

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, 30 people were identified with Burkholderia cenocepacia in 2023 (CF in Australia report 2023). 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 using glycoengineering to produce prototype vaccines, the team hopes to establish a scalable and inexpensive method to create Burkholderia-focused vaccines. If successful, this system will allow for the affordable and easy production of these vaccines, potentially leading to significant healthcare savings by both preventing and reducing Burkholderia infections. Dr. Scott aims to develop the first glycosylation-focused vaccine.

What are glycoconjugate vaccines?

In the age of COVID-19 we became familiar with different types of vaccines, especially the mRNA vaccines used against COVID-19. However, there are many other types of vaccines used to prevent diseases. For example, live attenuated vaccines such as the measles mumps rubella (MMR) vaccine, are used and involve the use of weakened forms of microorganisms to stimulate an immune response and protect against infection.

Dr. Scott’s team has focused on the development of a newer type of vaccines known as glycoconjugate vaccines, which use only parts of a pathogen—in this case, the sugar molecules from the surface of the bacteria. These bacterial sugar molecules are often part of the bacteria’s disguise to evade human immune detection. By joining (or “conjugating”) a harmless protein to these bacterial sugar molecules, the immune system can recognize both the protein and the bacterial sugars, helping it mount a protective response.

Glycoconjugate vaccines, are some of the safest and most widely used vaccines in human health. They have been used to vaccinate against diseases like typhoid, pneumonia, and meningitis. By using glycoengineering to develop vaccines containing Burkholderia-specific sugars, these vaccines will help the body produce an immune response to both control and eliminate Burkholderia infections.

How can vaccines help patients already infected with Burkholderia?

While vaccines are a powerful tool to prevent infections, they typically need to be administered before exposure to a pathogen. An alternative approach is to use the vaccine as a treatment that creates a “ready-to-use” immune response in the form of antibodies against the glycoconjugate vaccine itself. As part of their work Dr Scott and Professor Goddard-Borger’s team will generate and test antibodies stimulated by glycoconjugate vaccines in the laboratory to determine their antimicrobial activity as part of a pre-clinical model. By assessing whether these antibodies can help control infections, this work will explore if antibody-based therapies could be used to treat established Burkholderia infections.

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.

Claudia’s Project

In 2019, Matt Ryan’s world changed when his young love, Claudia Coll lost her battle with cystic fibrosis at just 18 years of age.

Following such a devastating time, Matt never imagined he would have cycled across New Zealand raising more than $36,000 to fund research into a lifesaving vaccine in honour of Claudia.

Aptly named Claudia’s Project, Cure4CF used funds raised by Matt to support this vital research into a vaccine that may protect people from infection caused by the deadly Burkholderia bacteria, the very bacteria that cut Claudia’s life short in 2019. This project is a continuation of that work and dedicated in memory to Claudia Coll.