Traditional Allergen Remedies vs. Pacagen: A Better Way To Live Allergen-Free

When it comes to dealing with cat allergies, many people may default to common and non-specific solutions, such as antihistamines (allergy pills), corticosteroids (nasal sprays), immunotherapy (allergy shots), or simply cleaning more frequently. But how do these traditional remedies compare to modern solutions that are specifically engineered to deal with cat allergens, such as Pacagen’s nanobody technology? 

Of course, all of these approaches aim to solve the same issue: uncomfortable symptoms that arise due to allergens. However, the extent to which they tackle this task varies drastically – especially when you consider how it feels to use each remedy.

The science behind an allergic reaction to cats, and why traditional approaches aren’t enough

Simply put, allergic reactions are caused by your immune system overreacting to something that shouldn’t normally be harmful. You can think of it as an oversight on your immune system’s part, where it sees a particle and thinks it’s some sort of dangerous foreign pathogen. In that sense, these particles are known as allergens.

In the case of allergies to cats, the culprit is an allergen called Fel d 1, which is produced in cat saliva. Since cats groom themselves so frequently with their tongues, they can quickly spread Fel d 1 all over their hair, which they shed all over the household.

When an allergy-prone person is first exposed to Fel d 1, their immune system launches a primary immune response. This is where white blood cells called B cells are pushed to undergo a series of selection and differentiation pathways, becoming memory B cells. These memory B cells are capable of recognizing Fel d 1 and will remain in the bloodstream for a long period of time. Continued exposure to the allergen causes some of these accumulated memory B cells to further differentiate into plasma B cells, which then produce large amounts of Immunoglobulin E (IgE) antibodies that are specifically sensitive to Fel d 1. Amongst other things, these IgE antibodies end up binding to mast cells, priming them for a future exposure to Fel d 1.

The next time the body’s exposed, a secondary immune response is triggered, and the now-abundant IgE antibodies would signal the mast cells to release certain chemicals throughout the body. These chemicals include the infamous histamines and cytokines, which are responsible for the resulting allergy symptoms, such as itchy eyes, stuffy noses, shortness of breath, and rashes.

Fel d 1 is an especially annoying allergen because of its natural tendency to form a tetramer (with four subunits). Due to the kinetics of the interaction between IgE antibodies and tetramers, this makes the secondary immune response trigger much more frequently. 

Normally, this immune response would be a good thing, since it ultimately stimulates and prepares the body to fight off potentially dangerous foreign invaders. However, in the case of Fel d 1 and other allergens, which are otherwise harmless, it’s unnecessary and inconvenient.

Knowing all of this, we can understand why allergy meds and allergy shots seem to be effective:

• Antihistamines

• As their name suggests, these medications block the activity of histamine receptors in the body. The end result is that your body won’t react as strongly to all the histamine that’s released due to the immune system’s mishap. Since histamines are primarily responsible for most of the immediate allergy symptoms, antihistamines tend to deal with the early response.

• Corticosteroids

• Usually in the form of nasal sprays or oral pills, corticosteroids act to reduce the production of cytokines, thereby mediating the inflammatory response. They also stabilize the mast cell membranes, limiting the volume of histamines and cytokines that are released.

• Immunotherapy

• Typically administered as shots, this treatment aims to reduce sensitivity to an allergen. In practice, it’s similar to desensitizing your immune system to Fel d 1 through repeated and controlled exposure. If done successfully, the IgE antibodies would grow desensitized to Fel d 1, no longer triggering the release of as much histamine. 

However, these traditional anti-allergen methods all share one glaring weakness: none of them act on the actual allergens being exposed to the system. In other words, they merely alter your body’s reaction to the Fel d 1 allergen – after the primary and secondary immune responses have already occurred. In the best cases, the relief is temporary and diminishing. In the worst cases, the relief doesn’t come soon enough, if at all.

The rise of nanobody research and its recent applications

In contrast, Pacagen took a different approach – one that would depend less on your body’s capabilities and more on modern science.

From the very beginning, scientists at Pacagen were solely committed to engineering something that could specifically target Fel d 1 particles, before they would even be exposed to people’s immune systems. Fortunately, proteins with this exact potential have already started gaining traction in other fields of study – especially cancer research.

In cancer research, a unique class of antibody fragments called nanobodies have recently been seeing major success, both as a diagnostic tool and as a therapeutic. Derived from the antibodies of camelids (such as alpacas), these nanobodies are praised for several reasons:

• Binding specificity

• Due to their structures, nanobodies are innately easier to modify for diverse formats. This means that each strain of nanobody can be engineered to only bind to one type of target. In the case of cancer research, this made nanobodies excellent for targeted drug delivery.

• Stability

• Compared to traditional antibodies which are relatively large and clunky, nanobodies have fewer complicated interactions within itself. This means that they’re easier and cheaper to engineer, while also being much more stable by nature. This stability ties into their excellent binding properties, and also makes them incredibly safe to deal with.

• Short circulatory half-life

• Amongst other things, nanobodies are also known to circulate for less time when exposed into the bloodstream. In other words, the human body is able to naturally get rid of nanobodies quickly and easily, making them ideal for various treatment methods.

All things considered, the scientists at Pacagen were convinced that these nanobodies would be the perfect candidate for a solution to neutralizing Fel d 1.

The modern development of Fel d 1-specific nanobodies and how they work

The team at Pacagen soon began the discovery process, starting with alpacas. Alpacas (and other camelids) are extremely unique in the sense that their antibodies are much simpler in structure than other antibodies: rather than having both light chain and heavy chain segments, camelid antibodies are heavy-chain-only. This simple structure makes it much easier to reliably isolate their variable domain regions, which would go on to be the templates for nanobodies.

By using these heavy-chain-only antibodies, the scientists were able to isolate and engineer a strain of nanobody capable of specifically binding to Fel d 1 with over 98% efficacy. More specifically, these nanobodies actively bind to Fel d 1 monomers (one subunit) and dimers (two subunits), preventing them from forming those hyper-allergy-inducing tetramers. The nanobodies will also “pull apart” existing Fel d 1 tetramers, forcing them to remain in their less active monomer/dimer form as a Fel d 1-nanobody complex. These Fel d 1-nanobody complexes are unrecognizable to an allergy-prone person’s immune system. The result: the secondary immune response wouldn’t trigger the release of histamines and cytokines, and no allergy symptoms arise.

[Left] Size Exclusion Chromatography for Fel d 1 without intervention: mainly seen as smaller dimers (peak at 9.658) and larger tetramers (peak at 8.333). [Right] Size Exclusion Chromatography for Fel d 1 when exposed to nanobodies: almost entirely converted to Fel d 1-nanobody complexes (peak at 9.217), which don’t trigger allergic reactions.

Pacagen’s nanobodies vs. other remedies: efficacy and side effects

While allergy pills and allergy shots still have their time and place, their non-proactive nature and lack of specificity makes them weaker options when it comes to dealing with Fel d 1. Moreover, due to their broad impacts across multiple bodily functions, most of these remedies have associated side effects.  

For example, antihistamines generally fall under two major categories, each with its own set of side effects. First generation antihistamines, such as Benadryl, have to cross the blood-brain barrier to interact with histamine receptors in the brain. This results in drowsiness, alongside other things such as low blood pressure and constipation. On the other hand, second generation antihistamines, such as Claritin and Zyrtec, are specifically designed to not cross the blood-brain barrier. While this foregos the drowsiness issue, these second generation antihistamines have still been shown to cause headaches, vomiting, and abdominal pain. This is mainly due to the antihistamine non-specifically binding to other receptors in the body.

In contrast, Pacagen’s nanobodies are exclusively engineered to bind to Fel d 1 particles outside of the human body, making them significantly more proficient, with little to no unexpected consequences or side effects. With proper application, the nanobodies’ effects can be seen before one’s immune system is exposed to the allergen. This is done with the Cat Allergen Neutralizing Spray, which easily disperses the nanobodies onto external surfaces that have accumulated Fel d 1.

[Left and Middle] Pacagen’s nanobodies neutralize allergens at binding affinities better than many pharmaceuticals. [Right] When allergens have additional activity, such as DER P1, which is an enzyme that cuts proteins (protease), Pacagen’s nanobodies can reduce allergen activity by more than 95%.