Diagnostic Reagents
Neutralizing antibodies – the immune system's Superhero
February 01 , 2021

Neutralizing antibodies – the immune system’s Hero


By Sebastian Fiedler, Lead Application Scientist Life Sciences at Fluidic Analytics


Infectious diseases—a problem of the past or the present?

Modern medicine has provided an exceptional set of tools to prevent and treat infectious diseases – conditions that used to decimate the human population with frightening regularity. As the world struggles to battle the COVID-19 pandemic, however, we are starkly reminded that infectious diseases are not merely a problem of the past.

It is not only global pandemics like COVID-19 that evade the tools of modern medicine. We are in fact fighting this battle every day and on multiple fronts.  Humans remain under constant attack by bacteria and viruses, and even in modern times these pathogens still cause the death of millions of people around the world each year.

How do you catch an infectious disease?

Infectious diseases are caused by a variety of pathogenic microorganisms including bacteria, viruses, fungi and parasites. These pathogens typically enter our bodies through our mouths, eyes, noses or open wounds.

Once inside our bodies, these microorganisms take advantage of their new favorable environment and quickly start multiplying. This process can severely damage and even kill the host cells resulting in visible and often well-described symptoms of specific diseases.

Luckily, our bodies are not wholly without defense because the pathogens trigger an immune response to help fight the infection. This activity unfortunately can also create collateral damage within the body, with fever, rash, inflammation, and general malaise all hallmarks of an active immune response.

Thankfully, modern medicine has delivered powerful antibiotics that are effective at supporting our own immune response across a broad spectrum of bacterial pathogens. The treatment of viral infections, however, has been much more challenging, and reliable therapeutics have so far eluded our best efforts. The most effective approach to fighting viral infections still is prevention by using vaccines that prime the immune system prior to a first encounter.


What happens when a virus enters the body?

When a virus enters the human body, it literally “goes viral”, producing as many copies of itself as possible. To do so, the virus exploits a cell’s own metabolism to release the new virus copies into the body, initiating the infection cycle over and over again. Once cells are infected, their natural function is badly impaired and, even worse, they often die. The resulting deficit of functional cells is the cause of tissue and organ failure, sometimes to an extent that is fatal.

But as mentioned earlier, our immune system does not leave us defenseless against viruses. To prevent a large-scale viral spread in our bodies, several innate mechanisms protect us at each stage of infection.

The first time we encounter a novel virus it typically avoids detection by the immune system and is able to enter a healthy cell.

At this stage, this now-infected cell will utilize its internal defense mechanism to display fragments of the virus on its surface using special receptor proteins. This display of virus fragments alerts the body that the cell is infected and activates the immune system to kill and eliminate the cell before the virus can spread.

In addition, the infected cells will also produce molecules, called interferons, which directly interfere with the process of viral replication to slow down the reproduction rate. Interferons also send a handy warning signal to nearby cells to alert them of the growing viral threat.

Antibodies – our best defense

The best defense against viruses, however, is to stop the infection in its tracks. This immune mechanism is made possible not by the cells themselves, but by antibodies which can identify and eliminate viruses before they start the infection cycle.

Over the course of our lives, our bodies produce thousands of different types of antibodies that comprise our antibody-mediated immune response. Antibodies are proteins that are produced by B cells, which are a specialized type of blood cell. Once produced, these antibodies patrol our circulatory system and tissues, ready to deal with the pathogens.

Antibodies have several mechanisms to prevent infections. They can either neutralize viruses directly to prohibit their entry into the host cell, or they can crowd around a virus to increase its visibility to other immune cells. Once bound to a virus, antibodies can also tag the virus for phagocytes, which in turn ingest and destroy the pathogen.

When a virus enters the human body, it literally “goes viral”,
producing as many copies of itself as possible.

Our antibodies’ ability to recognize and bind to pathogens starts with their structure. Fully assembled antibodies resemble the shape of the letter “Y”.

The top of the two “arms” of the “Y” is where the magic happens. Imagine the arms as thousands of different jigsaw-puzzle pieces that give each antibody a unique shape. Each of those antibody jigsaw-puzzle pieces has the potential to fit specific virus antigens while fitting poorly with others.

The better the antibody and antigen fit, the higher their affinity to each other. In other words, the stronger they bind to each other the more effective the antibody is at preventing infection by the virus.

Novel Coronavirus (COVID-19) Neutralizing Antibody Testing

Figure 1: The better the antibody and antigen fit, the stronger they bind to each other the more effective the antibody is at preventing infection by the virus.

How do neutralizing antibodies earn their superhero status?

To infect, viruses must first enter a healthy cell. They accomplish cell entry by binding to receptor molecules on the surface of their host cells. For example, SARS-CoV-2 utilizes so-called spike proteins on its surface for initial cell binding. These spike proteins fit perfectly to the shape of a receptor protein (ACE-2 receptor) typically found on the surface of human lung cells. Once the virus spike protein binds to the receptors of the lung cells, the virus enters and begins to replicate.

Virus-neutralizing antibodies are designed to interfere with this binding event. To prevent entry to lung cells, an effective neutralizing antibody resembles the jigsaw-puzzle shape mimicking the lung-cell receptor ACE-2. In fact, it displays an even better fit than the receptor itself, resulting in the virus surface becoming covered by antibodies. This in turn prevents the virus from entering the lung cells. Moreover, such antibody-covered viruses become very sticky and attract each other to form large virus clusters, which, unlike individual viruses, are more easily recognized by other immune cells.

Novel Coronavirus (COVID-19) Neutralizing Antibody Testing

Figure 2: Neutralizing antibodies bind to spike proteins on the surface of SARS-CoV-2 and prevent the virus from binding and entering the host cell. As each antibody can bind to two spike proteins from different viruses, the start forming virus clusters that can be better recognised and destroyed by phagocytes.

If antibodies offer such great protection, then why do some people become severely ill with COVID-19?

This raises the question as to why some patients experience mild symptoms of COVID-19 while others suffer severely, or even die from, an otherwise identical disease.

One hypothesis is that the progression and manifestation of the disease depends on the ability and strength of the antibodies in our bodies to protect us. It is believed that an antibody will be an effective neutralizer only if it fits perfectly to the shape of the spike proteins and therefore binds strongly to the virus (i.e., it binds with a high affinity).

If a patient’s immune system produces only lower-affinity antibodies (or even non-neutralizing antibodies that do not block the receptor binding site of the spike protein at all), cellular protection becomes compromised, even though the immune system might try to compensate by producing increasing amounts of these weak or non-neutralizing antibodies.


So are there tests that assess if we have neutralizing antibodies?

Although it is reasonably straightforward to determine the presence of antibodies in COVID-19 patients using standard but crude immunoassays such as ELISA tests, assessing the virus-neutralizing capacity of antibodies in patient serum still relies on a cell-based neutralization assays. Although these assays do assess whether serum antibodies have the ability to block replication of the virus, they have significant drawbacks. They often require live biological materials and strict biosafety regulations, and most importantly, they are slow.

Because they rely on the growth of living cells in culture, cell-based neutralization assays take several days to complete. During this time, a patient’s infection continues to develop. A multi-day wait for clinically actionable information could lead to several days of isolation from loved ones and absence from work at best; or a severe deterioration of symptoms and death at worst.

Another limitation of cell-based neutralization assays specifically impacts the development of vaccines and antibody-based treatments. Current cell-based neutralization assays cannot characterize and quantify specific antigen–antibody interactions, but rather provide a binary readout of whether or not neutralizing antibodies are present. Because this binary outcome does not provide insights in the mechanisms of action of vaccines and therapeutics, key information about the relative effectiveness of vaccines or antibody-based treatments could be missed.

No-fuzz detection and characterization in hours, not days!

COVID-19 with all its impact on people, societies and everyday life, is a stark reminder that there is an urgent need in modern medicine for a test that informs patients, clinicians and researchers—in hours, not days—about the presence and, more importantly, the quality of neutralizing antibodies in their blood samples.

To address this need, we have created a rapid, cell-free, virus-neuralization assay based on our in-solution technology and made it available on our Fluidity One-W Seruminstrument. The assay measures the binding interaction between the ACE-2 receptor and the SARS-CoV-2 spike protein, as well as the subsequent displacement of the spike protein in the presence of virus-neutralizing antibodies directly in patient serum, all within a couple of hours. Nanjing Norman Biological Technology Co.,Ltd

Novel Coronavirus (COVID-19) Neutralizing Antibody Testing

Figure 3. Our in-solution assay allows for the direct measurement of virus spike displacement from the ACE-2 receptor in the presence of neutralising antibodies.

We are excited that this easy and fast approach could make a positive impact on patients’ lives and help researchers, clinicians and biopharma companies to better understand protective immunity and develop more effective vaccine and therapeutics candidates to fight COVID-19 (more information on this test shortly).

Nanjing Norman Biological Technology Co.,Ltd is committing to offer comprehensive IVD solution covering self-developing and manufacturing raw material,reagent,equipment,get more COVID-19 Antibody Test Kit and Antigen Test Kit from https://www.normanbio.com.


Novel Coronavirus (COVID-19) Neutralizing Antibody Testing Kit (Colloidal Gold)




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