The Virus Busters

Marveling at the Old Technology of Antibodies

In case you haven’t heard – having become too sheltered-in-place – the United States and much of the rest of the world is in an epic battle against an enemy: an invisible enemy in the words of our President. Of this adversary he reassures, “It cannot overcome the dedication of our doctors, nurses, and scientists,”  adding, it will be vanquished “. . . sooner, rather than later. . . ,” by virtue of a tenacious American spirit, innovation and unrelenting determination.¹

News from the COVID-19 battle front appears hopeful, as scientists are successfully advancing technologies to leverage and release antibodies. Not just any antibodies will do – only those captured from the blood of people who have recovered from COVID-19 illness.

The simplest technology involves the administration of what is called convalescent plasma. This super-power fluid coming from the blood of infected-and-recovered donors is teeming with antibodies, from which the “invisible” enemy cannot hide. The objective of this therapy is to buy time for the beleaguered patient receiving these molecular warriors, until their own immune systems train and recruit a home-grown mini-militia that can take down the virus of its own accord.²

Other therapies entail the development of a more concentrated cocktail of antibodies, called hyperimmune therapy, which delivers an even greater punch. While this therapy (like convalescent plasma) is subject to supply limitations on the part of human and mammal donors, GigaGen, a biotech company specializing in the advancement of transformative antibody therapies, has an eye to develop antibody therapies to combat COVID-19 using recombinant techniques. These high-level techniques will enable researchers to capture and replicate  complete antibody libraries from recovered patients.

These man-made therapies – as impressive as they sound – pale in comparison to the original technology that generated the starting materials on which the new therapies depend in the first place. It might be worthwhile to visit the seemingly miraculous origins of these natural munitions, and how they go about the business of antigen³ patrol and annihilation.

The Building of an Army

Antibodies are produced from white blood cells called B cells, which complete their maturation from stem cells in red bone marrow. Every B cell produces a single type of antibody, thereby according the immune system a catalogue of as many as several billion different types,⁴ many of which are generated before the human host has had any significant exposure to antigens. While undergoing training as mini munitions factories, B cells acquire two skills: 1) immunocompetence – the ability to detect and unleash war on invading pathogens, and 2) self-recognition – the ability to not attack “self.”

Amazingly, these two competencies are carried out with such fidelity over the lifespan, that we are rarely even aware of them until either is compromised. Immunocompetent failure is evident when “self” cells go rogue and reproduce faster than the immune system’s ability to detect and destroy – such as the case with cancer. Allergies, type-1 diabetes, multiple sclerosis, and specific forms of liver cirrhosis⁵ testify as to the destructive power of the immune system when self-recognition mechanisms go awry. Fortunately, these conditions are relatively rare, as our physiologies enjoy for the most part remarkable surveillance and protection from B cells along with a host of other immune-system effectors.

Once B cells are battle-ready, they take up their watch posts in lymph nodes and tissues. With literally thousands of membrane-bound antibodies tethered to their cell surfaces, B cells in effect “lie in wait,” until an invading pathogen is ensnared

How Antibodies Work

Once an invisible enemy is detected, antibodies act as grand obstructionists, foiling their infection and reproduction. These Y- and at times T-shaped molecules are released en masse from a host’s B cells whenever such cells encounter nonself molecules. Typically these nonself antigens reside like red flags on the surface of bacterial and fungal cells, virus coats, or even the body’s own cells if they have grown cancerous. With B cells sounding the alarm, the dispatched munition of antibodies bind on these specific sites on the pathogen in a process called neutralization. The neutralized pathogen thereby has no means for gaining access into the hosts cells and tissues – as it has been foiled and obstructed.

If this heroic effort on the part of our mini molecular warriors were not enough, it is not all antibodies do. In binding to antigens, antibodies make the ultimate sacrifice by summoning warriors from other branches of the immune system, to come and annihilate both them and the offending invader in a process termed opsonization.⁶

With the invader effectively decapitated, the job of B cells is not over. In the progress of battle the weapons of immunological warfare have been further shaped and honed. Antibody mediating cells having undergone additional training are deadlier than ever, fitted with antibodies having greater specificity to the offending antigen. Finally, battle plans are communicated to what are now memory B cells, so that in the event of future antigen exposure, a secondary response will be more targeted and vigorous (which is exactly the function of vaccines).

The Mind Behind the Design

Thus, while the technologies being advanced from the brightest scientists and biotech companies for combating the invisible enemy – COVID-19 – are remarkable, their engineering  cannot compare to the ancient but far from antiquated technology found in the cellular machinery of the many diverse immune-system cells (of which B cells play just a part). Certainly this pandemic has generated in most an appreciation for the brilliance of those dedicated scientists looking to leverage the kill-power of antibodies in disease abatement. But let us not forget to marvel and stand in awe of the greatest biotech engineer of all, the one who designed these remarkable weapons of immunological warfare in the first place. In deference to our creator, we should all acknowledge as did the ancient Jewish nobleman, King David, that we are truly “fearfully and wonderfully made.”⁷

Notes:

1. Retrieved from: https://www.dailywire.com/news/trump-this-invisible-enemy-is-no-match-for-the-spirit-and-resolve-of-the-american-people

2. Cross, R. (2020). Searching for a coronavirus cure in the blood. C&EN Global Enterprise 2020 98 (14), 33-35 DOI: 10.1021/cen-09814-cover4

3. Antigen – any substance (usually a molecule or protein) coming from microbes, foods, drugs or allergens that the immune system recognizes as nonself or foreign.

4. Fanning, L. J., Connor, A. M., & Wu, G. E. (1996). Development of the immunoglobulin repertoire. Clinical immunology and immunopathology, 79(1), 1-14.

5. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5055585/

6. Derrickson, B., & Tortora, G. J. (2007). Introduction to the human body: the essentials of anatomy and physiology. J. Wiley & Sons.

7. Psalm 139:14. The Holy Bible – English Standard Version. Crossway.