Melbourne clinicians have identified a key barrier to phage therapy and a workaround.
Melbourne clinicians have uncovered a critical barrier to phage therapy and a fix, after Australia’s first Victorian case showed pre-existing antibodies can neutralise treatment, prompting a shift to routine immune screening.
Researchers from The Alfred and Monash University reported in Nature Medicine that the finding was already reshaping how the therapy is selected and delivered for patients with life-threatening, drug-resistant infections.
The work comes from VICPhage, a joint clinical program spanning The Alfred and Monash University.
It is among the first services in Australia to offer end-to-end phage therapy, from pathogen matching and clinical-grade phage production to bedside administration and trial participation, for infections unresponsive to standard care.
Phage therapy involves administering bacteriophages, viruses that selectively infect and lyse bacteria, as a targeted alternative when antibiotics fail.
Senior author Professor Anton Peleg, director of Infectious Diseases at The Alfred and Monash University, said the field had been forced to mature quickly under the pressure of escalating antimicrobial resistance.
“Phages were actually first used early in the 1900s, but were effectively cast aside with the introduction of antibiotics,” he said.
“As we now face the growing threat of antimicrobial resistance, research on alternative therapies such as phage therapy is critically important to modern medicine.
“The work we are doing builds on the foundation of generations past but takes advantage of the huge innovations in science and technology to harness its potential for personalised treatments that could revolutionise the way we treat infectious disease.”
VICPhage operates under Australia’s compassionate-use framework, with clinicians seeking approval from the Therapeutic Goods Administration for patients who have exhausted options and face threats to life, limb or function.
The index case detailed in Nature Medicine involved a 22-year-old with cystic fibrosis and severe, recurrent infection due to a near pan-resistant organism. It was their first patient case in 2022 and the first ever in Victoria.
Despite careful phage selection, the therapy failed to achieve bacterial clearance. First author Dr Fernando Gordillo-Altamirano explained how the culprit was identified.
“We discovered that phage therapy didn’t work in this patient because he had pre-existing antibodies against the phage,” Dr Gordillo-Altamirano said.
“These antibodies destroyed the phages before they could kill the infection.
“We were swiftly able to determine how to test subsequent patients to see if they already have antibodies against particular phages, in order to adapt our treatment.”
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Professor Jeremy Barr, from the School of Biological Sciences and Centre to Impact AMR at Monash University, co-leads VICPhage and leads the Monash Phage Foundry, where the clinical-grade phages were produced.
“This was a pivotal phage therapy case of a very difficult-to-treat infection,” Professor Barr said.
“What we have learnt here will allow us to provide faster and more effective phage treatments in the future.
“With collaborators around Australia, we are reviewing methodologies, phage production approaches, and data collection from treated patients across the country.
“There’s still a long road ahead, but it’s one we are determined to travel as this therapy has the potential to save hundreds of lives for patients suffering from serious and life-threatening infectious disease.”
The program is now standardising immune profiling, refining production methods and contributing data to multicentre efforts across Australia to harmonise protocols and accelerate evidence generation.
