Bacteriophages were first discovered in the early 20th century and noted for only their ‘antibacterial’ activity. iNtRON also has developed various anti-bacterial pipelines based on phages and endolysins (antibacterial protein derived from phages) which are in clinical trial stages. Now, iNtRON has moved onto its new step of using phage to target not only bacteria but virus as well. This all began with ViP Cycle theory. It is a theory to explain fundamental relationship between phage, virus, bacteria and human. The theory began with the hypothesis that there could be a closed interaction between evolution of phages and viruses, and phages and viruses share common regions in their genes. iNtRON believes these common regions are critical area where we should focus.
iNtRON utilizes bacteriophage’s bacterial lytic properties and functions and applies them to neutralize viruses that are harmful to humans and animals. This approach changes the existing paradigm that “bacteriophages are only applicable to bacterial infectious diseases”. We are expanding the scope of bacteriophages application to viral infectious diseases and developing anti-viral drugs and vaccines. iNtRON named this platform technology PHAGERUS® (Bacteriophage + Virus). PHAGERUS® means “Evolved-Bacteriophage as Anti-Viral Drugs”. It is iNtRON’s novel platform technology for the development of vaccines or therapeutics to target various human and animal viruses that cause pandemic infectious diseases. PHAGERUS® is being developed based on utilization of iNtRON’s unique “E2BID” (Evolved-Bacteriophage Bio-Informatics Drug) technology.
Based on the core platform technologies and rich experiences and know-hows over 20 years in the field of bacteriophage R&D, iNtRON has expanded phage applications to (1) PHAGERIA® (phageome-related field) and (2) PHAGERUS® (virus target field), and we are developing virus-related therapeutics and vaccines. We believe PHAGERUS® technology will suggest a new paradigm for anti-viral therapeutic and vaccine development.
The selected natural phages (including commensal phages and foreign phages) could trigger an innate immune response without engineering the phages.
iNtRON’s approach is to select more intensive and effective natural phage candidates from its phage library that share common regions with target viruses. These common regions will work as antigens to induce humoral immune response.
For the engineering to display target virus antigens to phage capsid surface, a suitable mockup phage is needed. Mockup phages should have no host immune response nor harmful toxin genes, and at the same time, should be favorable to be engineered and cultured. iNtRON has secured over 500 phage candidates in its BRB (Bacteriophage Resource Bank), and has found most suitable phage for the mockup phage candidates. After final selection of the best mockup phage candidate, target Virus antigens will be displayed on to the capsid surface of the mockup phages.
Induction of Adaptive Immunity by PHAGERUS®
The human immune system is divided into innate immunity and adaptive immunity. In general, most virus-related vaccines are developed to induce adaptive immunity. Adaptive immunity can be divided into humoral immunity and cell-mediated immunity. It is well known that both innate and adaptive immune systems are necessary to provide an effective immune response. Further, effective immunizations must induce effective stimulation of both the humoral and cell-mediated arms of the adaptive system in order for the human body to have an effective defense system against virus. iNtRON’s PHAGERUS®-based pipelines can trigger both humoral and cellular immunity at the same time by displaying antigen on the surface of phage capsid and also using phage itself as an adjuvant. By developing Ag-PHAGERUS® that induces humoral immunity and Adjuvant-PHAGERUS® that induces cell-mediated immunity, iNtRON’s PHAGERUS® technology will be a backbone of the first-in-class viral vaccine that can overcome the limitation of the conventional viral vaccines in the market, which induce only limited part of immune system.
As a New Vaccine Platform in the Post-COVID Era
After the break of COVID-19, it is expected that global vaccine companies will expand investments to develop a new vaccine platform technology. Accordingly, mRNA vaccine platforms in various types along with other new vaccine platforms will be developed. iNtRON’s PHAGERUS® technology can provide a new vaccine platform and can compensate for the shortcomings of existing vaccines, such as limitations as injections and side effects caused by the use of vaccine adjuvants. In addition, iNtRON is developing related technologies that can facilitate efficient manufacturing for successful commercialization. Speaking of the technical aspects, PHAGERUS® technology-based vaccines can induce mucosal immunity through eyes, nose, oral cavity, and sublingual, minimizing the risks and side effects of existing injectable vaccines and providing convenient administration method. Using mock-up phages or adjuvant, PHAGERUS® eliminates the need to use conventional adjuvant, avoiding the side effects of injectable vaccines and providing improved safety. PHAGERUS® technology presents a new paradigm to extend the application range of bacteriophages from bacterial targeting to viral targeting. Based on rich experiences and know-hows in phage-related original technologies and drug development for a long time, we will do our best to secure the strongest weapon in the battle for new virus vaccines and therapeutics-related source technologies in the post-COVID era.