Australian Phage Network

We have published and advocated phage therapy [1-7]. Here we describe our effort to build a national consortium aimed at delivering phage therapeutics, in an Australian context.

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Associate Professor Ruby CY Lin, Dr Ameneh Khatami, Dr Jessica C Sacher, Dr Pieter-Jan Ceyssens, Mr Jan Zheng, Dr Ali Khalid, Professor Jonathan R Iredell and the Australian Phage Network

Phage therapy currently means either empiric phage, or phage combinations (“cocktails”), with a broad spectrum of activity or the quick matching of phage/s to patient isolate for individualised treatment. Stability (shelf life) of phages alone or in combination, antagonism and synergy of phages and antibiotics, host responses to phage infusion, the pharmacokinetics, pharmaco-genomics and pharmaco-dynamics of therapy and its overall regulation and clinical implementation all present challenges. Nevertheless, an obvious first step is to develop large bank/s of phages and effective mechanisms to screen these against target isolate/s in a timely fashion. (We’ve outlined the trials and tribulations of setting up a phage biobank here, https://naturemicrobiologycommunity.nature.com/posts/59536-building-a-sustainable-phage-biobank-trials-and-tribulations.

Several high profile reports [7-11] are in turn driving industry investment in phage collections, with the global phage market projected to reach $1.4 billion USD by 2026 [12]. The underlying requirement common to all of these treatments has been the availability of safely-prepared phages with therapeutic properties. And yet, although thousands of phages are housed in research laboratories distributed globally, most labs are ill-equipped to prepare safe phage preparations for patients, and biotech companies with access to clinical-grade phage manufacturing are not readily able to access phages from researchers. Therefore, many treatable infections go untreated for reasons largely logistical in nature. Additional challenges are faced by clinicians treating children, where routine access to novel therapeutics, including phages, is often delayed [13].

The unmet need for establishing efficient phage research and development pipelines has never been clearer. Phage researchers and biotech companies around the world currently volunteer their time and resources to prepare phages in response to individual patient need [14-16], and yet nearly everyone expresses concerns that this practice, in its current ad hoc form, is at best unsustainable, and at worst may lead to unsafe phage applications that could compromise progress in the entire field. There is clearly a momentum now to build systems that drive integration and quality assurance of phage collections and preparations that can serve a global collective of clinicians, researchers, biotech companies and regulators.

Since our last blog on phage biobanking, we have developed a bit further in the phage research, clinical and biomanufacturing space, with a focus on optimal functions, key partners and systems, and sustainability of a phage biobank. Here we have a proposed roadmap for Australia’s first phage biobank and pathways to building the ecosystem to facilitate phage therapy initiatives in Australia (Fig 1). For example, a hub and spoke network model starts with the most experienced site, building capacity by sharing protocols, research and material. Clinical coordination and biobanking (of target microbes and candidate phages) link bio-surveillance to the supply chain. Tight coupling of the biobank to agreed protocols within the network is expected to accelerate research output, development of therapeutics and diagnostics and expedite clinical and regulatory processes (Fig 1).

 

Fig 1. Australian Phage Network

We noted the need for standardisation of terms and protocols. For example, Bacterial and Archaeal Viruses Subcommittee of the International Committee on the Taxonomy of Viruses establishes systematic nomenclature for phage genomes and consistent annotation for phage sequences [17]. This would facilitate accessibility of a biospecimen navigator platform and allows development of simple and efficient tools such as a “Phage Passport” [18-21], as demonstrated in Belgium’s Magistral Model [19]. Specifically, standardising quality parameters for the final phage product for distribution. The ‘phage passport’ may need to be defined within each jurisdiction but ideally would be globally competent, encompassing all jurisdictions requirements and using agreed common language and protocols. In an Australian context, we advocate a globally competent use of agreed common language and standardised administration and laboratory monitoring and follow-up protocols in order for phage therapy to be included in respective jurisdiction’s national formulary. By collaborating with international partners (e.g., Phage Directory, https://phage.directory/), this might reduce friction between stakeholders for maximum operational efficiency. Such ecosystems should serve to inform design of regulatory frameworks for phage therapy beyond immediate compassionate use, grounded on the bioethical principles of justice in healthcare that demands equitable access.

We are currently addressing ethical, legal, financial and governance, elements that are essential in all biobanking entities [22] but a user-pays cost-recovery model can help offset initial low utilisation, expand specimen collections and offset labour costs. There is a strong argument for public funds to support a public good, building on the community’s belief that good quality collection of biospecimens enhances biomedical research development and innovation [23].

In a broader context, support and collaborations from organisations such as the International Society for Biological and Environmental Repositories (ISBER) and the Biobanking and BioMolecular Resources Research Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC) are important to maintain sustainability. A globally coordinated phage biobanking network can assist in democratising access to phage therapy. In the Australian context at least, a networked phage biobank that identifies matched phage(s) for patient samples (personalised phage therapy) using NATA (National Association of Testing Authorities, Australia)-accredited diagnostic and identification services eligible for Pharmaceutical Benefits Scheme rebates, properly integrated with state and national surveillance programs, is the ambition.

Funding

Seed funding for NSW Phage Biobank (JI and RCYL) and NSW Microbial Biobank (JI, RCYL et al.) was awarded by NSW Health, NSW State Government, Australia. Data linkage funding with CHeReL  for the biobanks was awarded by the Ministry of Health, NSW State Government, Australia (JI and RCYL). Australasian Society for Infectious Diseases Research Grant for Phage Therapy in CF kids (AK, HS and RCYL).

Acknowledgments

We would like to thank the Australian Phage Network (in alphabetical order): Jeremy J. Barr, Nouri Ben Zakour, Kim Chan, Barbara Chang, Alicia Fajardo Lubian, Lucy Furfaro, Josephine Ho, Bernie Hudson, Anthony Kicic, Jian Li, Leszek Lisowski, Trevor Lithgow, Susan Maddocks, Angela Netluch, David Paterson, Ian Paulsen, Matt Payne, Anton Peleg, Aleksandra Petrovic Fabijan, Indy Sandaradura, Vitali Sintchenko, Peter Speck, Steve Stick, Carola Venturini, Morgyn Warner, Karen Weynberg; Phage Network International Partners: Ran Nir-Paz, Ronen Hazan, Rob Lavigne, Jeroen Wagemans, Heejoon Myung, Nikoline S Olsen, Lars Hestbjerg Hansen, Graham Hatfull and broader network; Shawna McCallin, Jean-Paul Pirnay, Petar Knezevic, Miguel Artuor Barreto Sanz, Tobi Nagel, Minmin Yen, Bob Blasdel, Chip Schooley; NSW Ministry of Health, Kerry Chant, Antonio Penna, Anne O’Neill, Laura Collie, Julia Warning; NSW Statewide Biobank, Jennifer Byrne, Adam Robinson, Jane Carpenter; Westmead Biobank, Judith Head, Joey Lai and Maggie Wang, WIMR bioinformatics, Brian Gloss; The Centre for Health Record Linkage (CHeReL), Usha Salagame and the UNSW Recombinant Product Facility, Christopher Marquis and Hélène Lebhar.

References

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    Ruby CY Lin

    Project Manager / Adjunct Associate Professor / Genomic Chair (Westmead Research Hub), Westmead Institute for Medical Research

    I help organisations build academic-industry hybrid teams. I have skill sets that are interchangeable between academia and industry. I have a proven track record of managing large scale multi-discipline projects within budget and time constraints. I am an effective communicator and collaborator, and have experience in mentoring, management and leadership. This is reflected in my capacity as a researcher where I was successful in securing over A$5.4 million research funding over the course of the last decade or so, and as the president of Australasian Genomic Technologies Association, a premier professional society in Australasia (2013-5). I am interested in implementing genomic (personalised) medicine into healthcare and better consumer health policy. My publications are available in ORCID (0000-0003-4163-511X), Google Scholar and Research Gate (>4000 citations), and I have >90 Internationally/nationally peer-reviewed conference presentations. My key skills are in the discipline of: Genomics, Transcriptomics, Cardiovascular Disease, Obesity, Cancer Biology, Animal models, Nucleic Acid technologies, microRNA, microRNA therapeutics, Systems Biology, Pharmacogenomics, Experimental Design, Budget project grants (strategic and translational perspective), Risk and feasibility assessment, Team Management, Mentoring, Establish networks amongst industry and academia (key stakeholders engagement) and of late ethics and governance for phage therapy clinical trials. I advocate for women in STEMM and do pro bono career coaching. I volunteer as a primary ethics coordinator and as a parent in the management committee for Out Of School Hours childcare at my kids' school, and I am a mentor for the Junior Science Academy holiday program at Macquarie University. During COVID lockdown I knitted beanies for friends and their babies and for colleagues. We also got a puppy since we are working from home. During the last 7 months I spent a lot of time on Zoom and eating chocolate (sometimes concurrently), as well as spending time writing grants and papers, and mentored/ing young scientists and clinicians who have reached out through LinkedIn.

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