Phage cocktail-based COVID-19 vaccine may have potential for much longer-term efficacy

Issue 122 | April 16, 2021
10 min read
Capsid and Tail

Photo credit: @hakannural, Unsplash

This week, we’re featuring an opinion piece by Dr. Mert Selimoglu (Pakmaya, Turkey) on phage-based COVID vaccines, and the opportunity he sees for using a phage library/cocktail approach to make more effective vaccines.

What’s New

Phil Huss (University of Wisconsin-Madison) and colleagues published a new paper in eLife describing their use of deep mutational scanning to map the functional landscape of the T7 phage receptor binding domain. Using this high-throughput, locus-specific phage engineering method, they systematically dissected the functional role of every residue in the tip domain of T7 phage RBP. This then allowed them to engineer T7 variants that were more highly active against E. coli.

Receptor binding proteinResearch paper

Janet Nale and Martha Clokie (University of Leicester) published a new perspective in Current Opinion in Biotechnology on preclinical data and safety assessment of phage therapy in humans. They emphasize that safety and efficacy data is needed to motivate clinical trials, how in vitro studies can ensure the most promising phages are developed, how human cell line studies can provide key data on human-phage interactions, and how insect and animal models can also inform phage development.

Phage TherapyResearch paper

One issue that obstructs phage efficiency in vivo is poor localization of phage to the site of infection. Aurelija Grigonyte (University of Warwick) and colleagues published a new paper in Pharmaceuticals showing how they modified phages to increase their association with lung epithelium cells in vitro.

Engineered phagesIn vivo interactionsResearch paper

Several high-profile phage therapy clinical trials have failed, leading many to point toward phage formulation and method of application as being of underappreciated importance. Daniel Rosner (Fixed Phage, Glasgow) and colleagues published a new review in Pharmaceuticals on formulations for phage therapy and potential uses of phage immobilization.

FormulationResearch paper

Ellina Trofimova (Macquarie University, Australia) and colleagues published a new preprint describing Plaque Size Tool: an automated command-line application for plaque analysis, which can simplify and standardize phage plaque morphology measurements.

PreprintTool

Latest Jobs

SponsorPost Doc
Cytophage Technologies (Winnipeg, Manitoba, Canada) is currently seeking a full-time Postdoc / Bacteriophage Synthetic biologist to work in their Research and Development department for a 2-year term with the possibility of extension. This position will report to Senior Research Scientists. Specific project work will include research in the development of alternative cloning / expression hosts for both episomal and chromosomal integration plasmids. Apply by April 30!

Community Board

Anyone can post a message to the phage community — and it could be anything from collaboration requests, post-doc searches, sequencing help — just ask!

We are excited to announce that we are holding a forum on Phage Therapy in the United Kingdom on the 22nd of April, 2pm-6pm BST.

This event will be focussed on planning the pathway to phage therapy in UK, starting with testing phage therapy for bacterial UTIs resistant to antibiotics, and developing the next steps for regulations and clinical trials.

Key speakers include Dr. David Jenkins from the British Society for Antimicrobial Chemotherapy, Prof. Krystyna Dąbrowska from the Polish Academy of Sciences, and more, discussing AMR, regulations, and previous experience with treatment.

Register now, and save the date!

Phage TherapyVirtual Event

The Africa Phage Forum is hosting its next phage webinar in its series, April 23 at 4pm GMT with special guest Dr. Jesca Nakavuma (Veterinarian and Senior Lecturer at Makerere University, Uganda), who will give a talk entitled Practical challenges and possible solutions in phage research — a question and answer session.

Register now for this event and/or the whole series at https://apf.phage.directory.

Virtual Event

Thanks to everyone who attended one or both of the PHAVES events we hosted this week! We heard Dr. Clara Torres-Barceló talk about phages for plant pathogens (recording here!), and Dr. Randy Fish talk about phages for diabetic foot infections (recording to be shared soon!).

Thanks also to those who attended our IBRC/Phage Directory bioinformatics seminars over the last few weeks, with Dr. Justin Clark, who told us about TAILOR’s pipeline for assessing safety of therapeutic phages (recording not available at this time), and with Dr. Jason Gill, who told us all about using the Center for Phage Technology’s instance of Galaxy to annotate phage genomes easily (recording here!).

Whenever we can, we publish recordings of our events on our YouTube channel here — subscribe to get notified here: https://phage.directory/youtube!

Virtual Event

Phage Club on Clubhouse has become a regular occurrence! These are casual audio-only drop-in chats; come for a few mins or stay the whole hour! Also, the new update means Clubhouse now supports Android too, not just iPhone!

Current rooms:

‘Phage Phwednesdays’ — Wednesdays at 9PM Eastern
Thanks to those who came this week for our ‘after party’ after Randy Fish’s diabetic foot / phage therapy talk! (Recording for his webinar to be shared soon)

‘Phage Phridays’ — Fridays at 1PM Central
This Friday special guests from the Eliava Phage Therapy Center joined to discuss their phage therapy methods and experience.

Email [email protected] if you need an invite to Clubhouse!

If you want to host your own room within Phage Club on Clubhouse, or suggest a theme or guest, we can make that happen! Let Jessica, Jan, Sabrina or Adriana know if you’re interested.

ClubhouseVirtual Event

PHAVES #16 will be May 12 at 2PM Mountain time. Dr. Greg Canfield and Dr. Laura Damioli from the University of Colorado will give a joint talk entitled: Freedom from antibiotic purgatory?: Salvage phage therapy for cure of spinal hardware infection.

Sign up for this event and future ones at https://seminars.phage.directory/!

PHAVESVirtual EventPhage Therapy

Hello everyone! My name is Melissa and I am a 3rd year grad student in the Biology department at the University of Alabama at Birmingham researching the mechanics of phage evolution. I am seeking obligately lytic phages that target Pseudomonas (preferably aeruginosa), E. coli or S. aureus for use in my evolutionary studies. Host bacterial strains for strain specific phage would also be appreciated.

I would also like to connect with researchers who have experience in culturing and infecting Pseudomonas. There are some quizzical results that I would love to discuss!

You can contact me at [email protected]. I appreciate all your help. Hope you have a wonderful day! Warmest Regards, Melissa

Seeking phages

Check out this YouTube explainer video by Dr. Sabrina Green, R&D Director at BCM Tailor Labs, entitled ‘Developing an Expedited Pipeline to Develop Phage Therapy for Multidrug-Resistant Infections’. Subscribe to their channel here for lots more where this came from!

ExplainerVideo

Phage cocktail-based COVID-19 vaccine may have potential for much longer-term efficacy

Profile Image
Cell Line and Process Development
Pakmaya, Pak Group of Companies
Skills

Biotechnology, Phage isolation, Molecular Biology, Data Analytics

He has an academic background in the generation and production of whole and recombinant antibodies via classic hybridoma technique and synthetic biology techniques, using phage display. Since 2016, he has been working in the R&D of a food biotechnology company with the role of industrial cell line and bioprocess development.

Phage Hosts

There is an apparent race in the development of the most effective vaccine against Covid-19 Pandemic (E. Callaway. Nature 580, 576-577; 2020). In addition to different approaches, we are also experiencing the introduction of mRNA based vaccines as a very fast to test and feasible alternative to produce comparing with the cell culture-based approaches.

Although vaccines developed via whole viral components show sufficient protection according to phase-II and early phase-III studies, their protection efficiencies are expected to be less than those generated via nucleic acid based (NAB) or viral vector based (VVB) vaccines due to the polyclonal response that they cause. On the other hand, thanks their monoclonal responses, high efficiencies has been reported for NAB or VVB vaccines, which use the high fidelity machinery of the human ribosomal system for in-vivo expression of the spike protein.

Since the beginning of the pandemic, there has been reported mutations on the spike protein and its prominent region called RBD (receptor binding domain) (L. Guruprasad. Proteins 89:569–76, 2021; Y. Huang et al. Acta Pharmacol Sin 41, 1141–49; 2020). Unfortunately, these accumulated mutations has a high potential to reduce or even stop the effectiveness of the NAB and VVB vaccines (E. Callaway & H. Ledford. Nature; 2021). From this point, we should consider in advance that there is a need to develop a cocktail vaccine that can meet all possible mutations, which may arise throughout such a pandemic.

There are some varieties regarding the phage-based vaccines in the current literature (A. González-Mora et al. Vaccines 8, 504; 2020). In addition, there is also a company, named Adaptive Phage Therapeutics, declaring their Covid-19 vaccine at phase-I study. They are pointing out the flexibility of the use of their vaccine in alternative routes such as mucosal and intramuscular, meaning that one can be able to use such a vaccine in oral and nasal routes in addition to intramuscular one as well. However, as it can be inferred from their statements, their vaccine was developed against only one variant of the virus. This means that this vaccine still has the potential to be eliminated with the emergence of the forthcoming variants. However, the use of a proven technique, phage display, in a different way could be expected to overcome such a limitation.

Bacteriophages displaying RBD on their surface, instead of an ScFv library, could be used for this purpose (L. Jespers et al. Nature Biotechnology 12, 899–903; 1994). Thanks to error-prone nature of the system, applying only one or two biopanning round on ACE-2 receptor, a variety of the epitope displayed on a phage cocktail can be collected and produced via a cost-efficient E. coli fermentation. In addition to its high biocompatibility and inherent adjuvant characteristics, these phages are expected to develop greater immune response than viral vaccines due to their better monoclonality. The production process provides also apparently a competitive advantage over the cell culture dependent methods. Besides, eliminating the risk of possible inefficiency in a long term as we are observing in NAB and VVB vaccines, such a cocktail is expected to be effective in the long term after completing the critical time consuming (pre)clinical trial phases.

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