In light of the novel coronavirus, scientists and researchers from all over the globe have been looking at traditional and non-traditional methods to develop a vaccine, some have led towards bacteriophages and Covid-19. Specifically in using bacteriophages to develop vaccines against the coronavirus.
Bacteriophage DNA-based nasal spray
At the University of Waterloo in Canada, researchers are in the process of developing a nasal DNA-based vaccine. The idea behind this vaccine is to stimulate an immune response in the nasal cavity and targeted cells in the respiratory tract. This will then trigger the production of a virus-like particle (VLP) that will induce an immune response. The VLP would attach itself onto the location which the Covid-19 would normally bind to, resulting in the limitation of sites for potential transmission.
Although the VLP will visually look similar to the SARS-CoV-2 in structure, it will be harmless. The similarity will help stimulate the body’s natural immune response against viral infection, which in return will help it battle against the coronavirus. Such an approach would help the body build natural immunity against the coronavirus and mitigate the severity of infections, which means that such a product would not only act as a vaccine but can also be used therapeutic.
Professor Roderick Slavcev says that once the DNA-based vaccine is complete, it can be administered using a nasal spray, that will deliver the medication which will help immunize and decrease the Covid-19 infections. Professor Slavcev has teamed up together with Emmanuel Ho, Professor at the School of Pharmacy, and Marc Aucoin, Professor of chemical engineering, those team will be designing the nanomedication itself, that will be delivered via nasal spray.
Researchers from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Freie Universität Berlin, Technische Universität Berlin (TU), Humboldt-Universität (HU), the Robert Koch Institute (RKI) and Charité-Universitätsmedizin Berlin, have chemically modified a bacteriophage capsid, that restrains a variety of viruses. During their research, it was observed that certain respiratory viruses were enveloped by the bacteriophage capsids, resulting in them becoming unable to infect lung cells. The results of this study are also being looked at the help battle the current situation with Covid-19.
The coronavirus, as well as other respiratory viruses, are dangerous as current antiviral medication only has a partial effect after infection. The ideal approach would be to prevent infection altogether. The research from Berlin, gives hope into such an approach, by having the phage capsid envelop the virus, leading to disabling it from infecting cells.
Professor Dr. Christian Hackenberger, Head of the Department Chemical Biology at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) and Leibniz Humboldt Professor for Chemical Biology at HU Berlin explained that pre-clinical trials have shown that they were able to render both seasonal influenza viruses and avian flu viruses harmless, which their chemically modified bacteriophages. This can possibly open up a whole new world of prospects in the field of antiviral drugs.
The bacteriophage capsid inhibitor makes full use of a feature that all respiratory viruses have in common, the trivalent receptors. These receptors, referred to as hemagglutinin protein, are used to attach to the sugar molecules found on the surface of a cell, such as those of lung tissue. When infection occurs, viruses hook onto the victim’s lung cells. It is this function of attachment which had the researchers, six years prior, to question whether there was the possibility of creating an inhibitor that would bind to the trivalent receptors perfectly. What was once an idea has today become a very real possibility with the development of the Q-beta phage, produced from the E.coli bacteria at TU Berlin, which is perfectly equipped with ligands, in this case with sugar molecules to act as bait.
Dr. Daniel Lauster, a former Ph.D. student in the Group of Molecular Biophysics (HU) and now a postdoc at Freie Universität Berlin explains that the phage is not infectious and is made of 180 identical proteins that are paced identically as the trivalent receptors on the surface of the virus. This creates an ideal scenario where the virus is deceived and attaches itself to the phage, followed by being enveloped and deactivated from further infection. Professor Hackenberger believes that taking this approach, which is non-toxic, biodegradable, and non-immunogenic, can open doors to battling other viruses and possibly even bacteria.
Bacteriophages and Covid-19 – Fighting secondary bacterial infections
No official recommendations have been looked at for the use of bacteriophages in the prevention of secondary bacterial pneumonia and sepsis that occurred in some patients. Although international researchers are looking towards phage therapy in battling bacterial secondary infections. The bacteria that begin to manifest during lung injury and the presence of the cytokine storm is still a prominent problem that has not been addressed. Lytic bacteriophages against such bacterial infection when using an inhalation method would be worth exploring. In addition, any prophylactic lytic phages have immunomodulatory effects that would be helpful for the prevention of cytokine reaction from the start.
Unfortunately, in the current situation, a study using phages can currently only be placed into action in Russia and Georgia, two countries with bacteriophage production, and the use of phages in daily practice. Russia also has a lot of experience with the preventive use of phages in times of natural disasters on a large number of people. In Europe and the United States, there are questions towards the production of phage preparations, but to date, there is no relevant legislation. The recommendations of WHO towards possible approaches against the superbug, unfortunately, contain no mention of bacteriophages.