A very special cocktail
Dear reader. A very warm welcome to the “A Look Inside IpA” blog.
This new blog series commences to communicate more elaborately, more directly, and more personally with you because social media platforms do not always provide an adequate forum to share new insights and perspectives on company developments and important topics related to the scientific field in which we work. This is an opportunity to provide you with a sneak peek into our “kitchen” so to speak: the work in our laboratories, the products in the pipeline, and what is happening inside IpA. We want to show you what motivates us and how we educated ourselves for the choices we made, and we want to make you a part of our exciting scientific journey. We want to share our astonishment over the complexity, but above all, the beauty of life, even when it derails into disease. It has made us modest, but also motivated, to develop interventions with respect for all of nature’s wonders.
A new viral kid on the block has ravaged the world as we knew it. However, the world is increasingly learning to deal with SARS-CoV-2 on the fly. Our company is inspired and well-equipped to do its share to overcome the public health threat using scientific rigor, informed through experience, in our high-quality laboratories.
Mass vaccination and boosting have changed the course of the SARS-CoV-2 pandemic and the word is out that the pandemic is becoming endemic. SARS-CoV-2, which causes COVID-19, is here to stay as an ongoing threat to public health. Of added concern, a very large group of underserved, immune-impaired individuals are at risk of developing severe disease when they contract the virus. We understand that effective, sustainable interventions are needed to keep all people safe – including the vulnerable immunocompromised population - and to protect our societies from another ravage.
It takes more than a vaccine to cope with a world-disrupting coronavirus. This virus mutates constantly, and this is not a surprise. All organisms on earth do this at a certain pace, but this type of virus, a ribonucleic acid (RNA) virus, typically does this much faster. The mutations caused by this so-called genetic drift are, in most cases, not beneficial for the virus at all. Every now and then, however, among the trillions of virus particles, a mutation or several mutations give a new variant an advantage over other strains. This likely means that it has become more contagious than its brother and sister variants.
In this blog, we explain our PolyTope® TATX-03 strategy in the development of a product that will help to protect us against an enduring risk of COVID-19.
Many infections start with a specific attachment of a virus to a certain biomolecule within the host; this is not different for SARS-CoV-2 and in this case the host is a human being. The SARS-CoV-2 virus must find its “docking site” to do its harm. This is a protein called angiotensin-converting enzyme II (ACE2). The ACE2 resides on human epithelial cells, including those lining the surface of our airways. A characteristic viral protein, the spike-protein, is responsible for binding to the ACE2 and the following entry of the virus into the cell where it can start its devastating action. This large and conspicuous spike-protein on the surface of the virus plays a key role in the etiology of COVID-19. It is not a surprise that nearly all involved pharmaceutical companies target this protein when developing a product to prevent or treat an infection from SARS-CoV-2.
One way to disrupt the function of the spike protein is to hinder its ability to bind to ACE2. Then, the virus is handcuffed, and unable to dock and do its harm. Most, if not all, proposed therapies to prevent infection are targeting this interposition of the spike protein. ImmunoPrecise employs this strategy as well but has weaponized its solution much more effectively than others. We explain this below.
ImmunoPrecise is an antibody company and our antibodies, like all others, bind specifically to an antigen. In this case, the antigen is the SARS-CoV-2 spike protein. Antibodies pick out parts of the antigen, which are called epitopes. These epitopes may change by mutation and, as a result, the antibody may lose its ability to bind to the mutated epitope as the binder cannot recognize it anymore. You may understand that the virus, which is no longer bound by a neutralizing antibody, has a replication advantage over a variant that is still recognized by such an antibody. In fact, Omicron and other variants-of-concern (VoCs) most likely surfaced because of this process. Similarly, this mutagenic escape rendered several commercial immunotherapies useless as the conditional market approval of some of these antibody-based therapies was restricted due to their failure to neutralize Omicron.
ImmunoPrecise employs this strategy as well but has weaponized its solution much more effectively than others.
We were always fully aware of the viral evasion risk and ImmunoPrecise has discovered an ensemble of antibodies which show unprecedented resilience to this viral selection process. The discovered antibodies in our TATX-03 cocktail bind simultaneously to multiple key antigen epitopes, including the ones which are less likely to change. The epitopes are distinct and not overlapping. They are scattered over the entire spike protein, and not just the part of the ACE2-binding domain (RBD). You may now start wondering why IpA is not only relying on handcuffing the most important offensive weapon of the virus, namely the RBD. That is because we also want TATX-03 to recruit the body’s own weaponry to combat infections. We believe that this approach is imperative to design a sustainable therapy with powerful efficacy in humans.
One of the reasons to recruit and activate the body’s own weapons is that we are aiming for an essential function, which antibodies have in ‘real life’. In other words, antibodies do not only bind to an epitope, but also blow a “warning whistle”. Our body is attacked continuously, and many organisms and viruses enter our system regularly. It is another astonishing wonder of mother nature to recognize an intruder and mark it for clearance by recruiting an arsenal of soldier cells and by activating the body’s chemical weapons. When bound, the antibody induces several processes that inactivate, degrade, and clear a foreign micro-organism or virus. Due to the simultaneous binding of multiple antibodies to the spike protein, TATX-03 is also anticipated to clear SARS-CoV-2 via the body’s own armies. The antibody blend not only blocks binding to the ACE2 but likely activates antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and/or complement-dependent cytotoxicity (CDC).
The antibodies in the TATX-03 cocktail collaborate and neutralization of the virus in SARS-CoV-2-challenged animals is much better than when the animals only received a single or fewer therapeutic antibodies in combination (combinations of 2 or 3 antibodies). Although this was our aim, we were delighted to see how well our ensemble did its job. The PolyTope® TATX-03 antibodies work together, and we are making efforts to further unravel the exact mechanisms behind the observed phenomenon.
The antibody discovery experts in ImmunoPrecise’s laboratories are looking at a successful mission and have passed the torch to their colleagues in development to finally bring the product to the people, and to help relieve humanity from an unpleasant and unwelcome virus with its ill-making qualities.
Concluding:
- The PolyTope® TATX-03 is a cocktail of antibodies preventing evasion by modifications in the virus’ genetic material which may change the antigenic activity of its key spike protein.
- The PolyTope® TATX-03 antibodies work in concert and together trigger effects which are more than the sum of each antibody constituent.