Ask the Experts
My cousin just had to go to the hospital after contracting the COVID-19 coronavirus. This morning, they put him on a ventilator and my aunt and uncle are an emotional wreck. His prognosis is not good because of a couple underlying conditions, but I just read today that researchers are having success with monoclonal antibody therapy for COVID-19 and would like to know more.
What are monoclonal antibodies, and where can my family get some? Are they approved for use yet?
Essentially, monoclonal antibody therapy for viral infection involves generating an antibody molecule type that reacts with the virus. This is a kind of protein that can lock onto and disable a virus or "antigen." A successful antibody does usually one of two things:
- It blocks the virus from entering cells, and
- On some occasions it may trigger the immune system to destroy the virus.
Most prominently, the effect is the first – that is, blocking the virus from entering cells. It doesn’t matter if the virus is circulating in your system if it can’t hijack your cells. It can’t reproduce, and your body will eventually clear it.
I don’t want to overstate it, though; antibody therapy is a bridge method to help the body respond to the virus – it may augment the body’s immune response.
In some patients this may be very successful; in others, not.
Serum Antibody Therapy vs. Monoclonal Antibody Therapy
Serum antibody therapy is based on antibodies in plasma from donors who beat COVID-19, while monoclonal antibodies are produced in a lab.
Phlebotomists, lab workers, and doctors collect and purify blood from convalescent donors to make serum antibody therapies for injection into patients with a weaker immune response. Serum antibodies, in general, are antibodies generated by the body against foreign antigens, like viral proteins.
Antibodies can be of multiple types, like IgG, IgM, or IgA, for example. These antibodies have many different targets, i.e., antigens they respond to.
In contrast, monoclonal antibodies are generated in a laboratory to react against a single antigen type, for example, a receptor or antigen site on the surface (like a spike protein) of the coronavirus.
To state it simply, serum antibodies are multiple and diverse, whereas monoclonal antibodies are singular regarding the number of antigens they target.
The human body produces antibodies in a general way, firing off antibody combinations in a bid to find the most effective one, while the ineffective ones circulate in the body and eventually are metabolized.
In worse scenarios, these antibody molecules can be partially responsible for inducing harmful symptoms, and in some diseases, people can experience serious complications from an over-active, but ineffective immune response.
Scientists developing monoclonal antibodies, however, generate one specific, effective molecule that, ideally, is tailored to the virus from the outset and doesn’t cause a harmful immune response.
A good way to understand the concept is to think “analog vs. digital.” When your immune system encounters a virus, like the SARS-CoV-2 virus that causes COVID-19, it immediately starts an “analog” cascade of chemistry, forming sometimes hundreds different antibody molecules in a bid to figure out some that fit with the virus like a puzzle piece and renders it ineffective.
That’s partially why serum antibody treatments are so often spotty and may have side effects. The treatments are based on collecting blood from people with a strong coronavirus immune response with multiple antibodies, and then purifying the blood until mainly only plasma containing the antibodies remains.
Even when the blood-type proteins are scrubbed out and specialists take other measures to purify the serum, it still can cause problems with people who have a different blood type than the serum donor, and the uncertain nature of the antibodies in the serum can cause serious allergic reactions and other problems.
Monoclonal antibodies, on the other hand, are tailor-made for a specific virus – as with binary coding of information in a digital signal; there is less “static,” i.e., adverse reactions to untested molecules.
Regeneron’s antibody cocktail contains two different synthetic antibody types that each target different sites on the virus to disable it. That’s because the virus spike protein – the pointy receptors that dot the coronavirus’ outer casing and look like a crown or “corona” – can have small alterations that affect how strongly the virus interacts with the antibodies.
If you use two antibody types targeting different receptor sites, you have a better chance of effectively foiling the virus, despite protein differences and resistance mutations characteristic of different SARS-CoV-2 strains.
Eli Lilly, another drug company experimenting with monoclonal antibodies for COVID-19, added a second antibody to their therapy midway through a clinical trial for this reason.
How soon will monoclonal antibody therapy be available for COVID-19 patients?
According to the Regeneron data we have now, manufactured monoclonal COVID-19 antibodies seem very effective in specific circumstances – namely in COVID-19 positive outpatients who don’t need ventilators. Tests are ongoing in populations with more serious coronavirus infections – the trials underway are conducted by pharma companies Regeneron and Eli Lilly.
Regeneron released the pre-publication results of the 275-person part of their trial, and Lilly said Regeneron’s results mirror their own (though Lilly hasn’t pre-released much data related to their trials.
None of the data released is robust enough to show the therapy works reliably in moderate and/or severe COVID-19 infections; it only suggests it may reduce viral levels and improve symptoms in non-hospitalized COVID-19 patients.
The companies were in talks with the FDA in October about whether the antibody cocktails should be released for emergency use against COVID-19, according to the magazine Science.
That doesn’t mean all the patients who need or want monoclonal antibody therapies for COVID-19 will get them, even if the FDA gave full approval for general use tomorrow.
Making safe and effective monoclonal antibodies
Cells have to genetically engineered to produce the desired monoclonal antibody. Viral antigens (like SARS-CoV-2 spike proteins) are injected into animal cells, and the B cells that produce antibodies are mixed with myeloma cells so that hybrid cells form in cell cultures.
These individual hybrid cells produce a monoclonal antibody and are cloned to make more cells that pump out antibodies.
Researchers have to propagate different cell lines and test their antibody products against the virus in a petri dish. The antibodies that work the best against SARS-CoV-2 are documented, and the cells that produce them are further propagated, while the ones producing weaker antibody molecules or less of them are culled.
Once these monoclonal antibodies are produced in quantity, they must be approved for safety and effectiveness in clinical trials and approved by the FDA for use.
As a result, any monoclonal antibody therapy is expensive and faces production hurdles that will make it difficult to scale in time for the medicine to reach everyone who contracts COVID-19. It’s not a simple matter of inventing a chemical and producing at scale via assembly line.
Further clinical trials with peer reviewed, published results will let us know how well this bridge treatment really works. Until then, we can hope the severe COVID patients participating in the current trials show a good response to the therapy.