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Centenary Institute - Medical Research
Centenary Institute - Medical Research

10 News features COVID-19 vaccine project

A collaborative project between the University of Sydney and the Centenary Institute to find a COVID-19 vaccine has been featured on 10 News.

The innovative research, focused on using the tuberculosis vaccine Bacille Calmette-Guérin (BCG) together with major components of the SARS-CoV-2 virus has seen promising early results in pre-clinical testing.

Lead investigator of the project Professor Jamie Triccas from the University of Sydney was interviewed for the story as was project co-lead Dr Claudio Counoupas, research scientist at the Centenary Institute.

View the 10 News story here.

Read more about the COVID-19 vaccine project here.

Sydney researchers test tuberculosis vaccine combination for COVID-19

A University of Sydney news article.

Design uses existing tuberculosis vaccine as key component.

Sydney researchers are taking an innovative approach to designing potential COVID-19 vaccines – using a tuberculosis vaccine to deliver components of the SARS-CoV-2 virus. Early results from pre-clinical testing in mice are promising.

Researchers at the University of Sydney and Centenary Institute are repurposing an existing tuberculosis vaccine to see if it can be used in a new way against COVID-19 to develop a novel vaccine.

The vaccine candidate, which Australian researchers have called BCG:CoVac, combines the vaccine for tuberculosis, Bacille Calmette-Guérin (BCG) with major components of the SARS-CoV-2 virus. The SARS-CoV-2 virus is the pathogen that causes the COVID-19 disease.

The study is part of a collaboration between the University of Sydney and the Centenary Institute to examine the immune response created by new vaccine candidates, including BCG:CoVac.

Lead investigator Professor Jamie Triccas, from the School of Medical SciencesFaculty of Medicine and Health, and the Charles Perkins Centre (pictured left) said the team was motivated to apply their expertise in studying vaccines to assess the effectiveness of this new formulation.

“We have over two decades of experience in the development and testing of tuberculosis vaccines, which will be applied for the assessment of BCG:CoVac,” said Professor Triccas.

“There have yet to be studies published that combine BCG and components of the SARS-CoV-2 virus as part of a new vaccine design, and we’re excited to test their potential.”

Early results promising

The researchers’ early unpublished results from pre-clinical testing in mice show BCG:CoVac stimulated an immune response aimed to control virus infection in humans.

In mice vaccinated with BCG:CoVac, the vaccine induced high levels of SARS-CoV-2-specific antibodies. The role of these antibodies is to bind the virus and help eliminate it from the body. The vaccine also triggered a strong anti-viral response by T cells (a type of immune cell).

Both these types of immune responses are thought to be important to ensure clearance of the SARS-CoV-2 virus from infected individuals.

Importantly, preliminary data also showed BCG:CoVac did not create high levels of inflammatory responses, which is a common barrier and concern in vaccine design.

“These initial results are very promising. BCG:CoVac is making the type of immune response that we predict is needed to control SARS-CoV-2 infection in humans,” said Professor Triccas.

“We are currently determining how well the antibodies generated after vaccination can ‘block’ the virus from infecting cells and thus provide protection from disease”.

Using the TB vaccine as a vehicle

In BCG:CoVac, the BCG vaccine is used as a vehicle to deliver distinctive proteins that originate from the SARS-CoV-2 virus surface. The goal is for the human immune system to develop a memory of SARS-CoV-2 and develop immunity.

There is currently global interest in the BCG vaccine, which is being investigated in ongoing clinical trials as a possible intervention to protect vulnerable people during the COVID-19 pandemic.

This is because of suggestions the BCG vaccine has other beneficial effects on the immune system that could protect against other infections. A 2019 observational study reported the vaccine is related to fewer deaths from certain infections other than from TB in low-income countries.

However, current COVID-19 related studies only investigate the protective effects of the BCG vaccine by itself.

Dr Claudio Counoupas, research scientist at the Centenary Institute and co-lead on the project, said: “Combining a part of the SARS-CoV-2 virus with BCG is key to this new vaccine.”

“This provides a specific ‘memory’ immune response against the virus that could provide long-term protection against disease. Our on-going studies will determine how long the  immune response lasts after vaccination in animal models. This is important information for future human testing of our vaccine.”

Professor Triccas said animal studies were necessary to ensure the vaccine is inducing the right type of immune response.

“These are critical before moving any candidate vaccine into human clinical trials.”

COVID-19 research targets human enzymes

Centenary Institute researchers have examined the critical role of human enzymes and the coronavirus in a newly published scientific review article that explores potential strategies for COVID-19 disease treatment and management.

The review article published in the prestigious ‘Journal of Diabetes’, seeks to explain how the human enzyme dipeptidyl peptidase (DPP4), which is a driver of diabetes severity, could be exacerbating COVID-19.

“COVID-19 is more severe in people who have type 2 diabetes, obesity and related chronic diseases,” says Professor Mark Gorrell (Head of the Centenary Institute Liver Enzymes in Metabolism and Inflammation Program) and senior author of the review article.

“We also see more DPP4 made in people with diabetes, obesity and related chronic diseases. Drugs that target DPP4 enzyme activity are regularly taken by many people for type 2 diabetes. Such drugs may have immune system and cardioprotective effects that could be beneficial in COVID-19 cases,” he says.

The review article notes that DPP4, which is known to be the key receptor for the MERS-coronavirus (Middle East respiratory syndrome) might also be an additional or alternate port of entry for SARS-CoV-2 into human cells.

“COVID-19 is caused by the SARS-CoV-2 coronavirus, which is similar to SARS-CoV and MERS-CoV. Each of these viruses attach to and enter human cells by binding to specific human enzymes,” says Professor Gorrell.

“Recent research suggests that SARS-CoV-2 can bind to both DPP4 and the ACE2 enzyme and so have two ways to infect our lungs and gut. Once we fully understand this process, we may be able to develop a drug that can help disrupt this viral activity,” he says.

Professor Gorrell, an expert in human proteases (enzymes that break down proteins) has recently launched a new research program in response to the growing COVID-19 pandemic.

“TMPRSS2 (Transmembrane protease, serine 2) is essential for SARS-CoV and SARS-CoV-2 infection. This protease activates the viral protein on the coronavirus necessary for virus cell entry at the start of viral infection in the human body,” he says.

“We are looking to develop a selective TMPRSS2 inhibitor that is both effective and very safe using our expertise and a unique drug screening approach. The successful development of such an inhibitor could be utilised as a novel therapy for both past and current, and possibly future, SARS-CoV coronaviruses.”

“I’m optimistic that our research will contribute meaningfully to the global COVID-19 health response,” he says.

Read the full media release here.

Further Information on the Centenary Institute’s coronavirus activity can be found here.

Centenary Institute investigates pre-vaccine treatments for COVID-19

Medical researchers at the Centenary Institute have focused their efforts to understand how the coronavirus is causing COVID-19 and are launching projects that will investigate a range of potential treatment strategies.

“Since the prospects of conventional antiviral drugs and vaccines are uncertain it is vital to develop other approaches that can prevent severe infection or reduce the long term health impacts resulting from COVID-19. This is our critical focus and attention,” says Professor Mathew Vadas AO, Executive Director at the Centenary Institute.

Professor Vadas believes that the Centenary Institute, a leader in inflammation, respiratory, infectious and cardiovascular disease research, has the unique expertise and facilities required to develop effective treatments for COVID-19, especially for more vulnerable people.

“Our world-leading research teams, together with collaborators from the University of Sydney, UTS, Sydney Local Health District, the Heart Research Institute and the Woolcock Institute of Medical Research are addressing three major areas,” he says.

  1. Understanding why the lung is so susceptible to the coronavirus (COVID-19 can induce acute respiratory distress leading to death).
  • Developing methods of understanding with a focus on reversing the devastation that the virus has in susceptible individuals including the elderly, males and those with pre-existing chronic diseases.
  • Developing novel therapies by using non-conventional, state of the art technologies and techniques.

Professor Vadas has confidence that this multi-pronged research program approach will contribute significantly to the reduction of the severity and impact of the disease on patients.

“Until an effective vaccine for COVID-19 is developed, therapeutic treatments are the best hope we have of getting on top of this pandemic, preventing harm and saving lives,” he says.

Read the full media release here.

Further Information on the Centenary Institute’s coronavirus activity can be found here.

Q&A: COVID-19 and genetic heart disease

Professor Christopher Semsarian AM, Head of the Agnes Ginges Centre for Molecular Cardiology at the Centenary Institute and Dr Michael J. Ackerman, M.D. (Mayo Clinic) have jointly participated in a live Q&A session on the topic of COVID-19 and genetic heart disease.

Hosted by the Sudden Arrhythmia Death Syndromes (SADS) Foundation the live chat covered key advice relating to the SADS community and the developing coronavirus pandemic. Questions from members of the public were also answered by the two cardiovascular specialists.

A recording of the session can be viewed online at any time at the following link: https://youtu.be/GmG_3IwyOfQ