Story at a glance
- New studies suggest that a combination of many different antibodies may prove useful at neutralizing the SARS-CoV-2 coronavirus.
- If turned into a treatment, it would have to go through clinical trials.
- Experts are hopeful that a monoclonal antibody treatment that uses several types of antibodies could be effective.
We’re finding out more about the coronavirus and COVID-19 every week, and lately there have been reports that fewer people than expected may develop antibodies to the virus after infection. Experts are still hopeful that synthetic antibodies may one day be used as a therapeutic for the coronavirus.
A study recently published in Nature identifies a mix of 19 different antibodies that target SARS-CoV-2, the coronavirus that causes COVID-19. Several studies like this have been published since the start of the pandemic, and some experts are hopeful that synthetic antibodies that mimic the natural antibodies could be used as a treatment for COVID-19 in the future.
The Columbia University research team collected antibodies from five people who were sick with severe cases of COVID-19. They identified 19 antibodies that “potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency,” according to the paper. These antibodies can bind onto the coronavirus in the areas where it attaches to human cells in order to get inside and replicate. The antibodies bind to two major areas at the top of the spike protein on SARS-CoV-2 called receptor-binding domain (RBD) and those to the N-terminal domain (NTD).
Antibodies as a treatment
Ever since the genomic sequence of SARS-CoV-2 became public information, people started working on developing vaccines and treatments for it. One type of potential treatment is antibodies that can attach to specific areas of the coronavirus to prevent it from being able to enter cells in our body.
Antibodies are proteins produced in response to a foreign particle in the body. They can be harvested from blood donations of people who have recovered from COVID-19 or they can be man-made in the laboratory based on the genetic sequences available. However, synthetic antibodies may be expensive to produce and it would need to be tested for efficacy.
Which is why these recent studies are interesting. Instead of focusing on one or two types of antibodies, researchers are identifying dozens of different antibodies that could work in concert to neutralize SARS-CoV-2. Part of the reason why the researchers were able to isolate such a variety of antibodies is because the patients they studied were sick for longer. “We think that the sicker patients saw more virus and for a longer period of time, which allowed their immune system to mount a more robust response,” says study author David Ho in a press release. “This is similar to what we have learned from the HIV experience.”
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A potential treatment
Monoclonal antibodies are artificial antibodies made in a lab and derived from a single B cell. They cannot replace a vaccine. Antibodies are like a drug: They are only helpful as long as you are taking them. And, more importantly, they do not give you immunity. For vaccines, “What you would like is to have some blood measure that serves as a correlate of that protective efficacy or immunity,” says Sarah Fortune, the chair of immunology and infectious diseases at Harvard’s T.H. Chan School of Public Health, to STAT. “Which sounds like it’s simple, but it’s much more complicated than you’d think.” But for antibodies, they can help people get over an infection.
Monoclonal antibodies have become an important type of treatment for diseases over the past several decades. Another study published in Nature shows that monoclonal antibodies may be able to reduce viral burden in two mouse models and protect against infection in macaques. This suggests that giving antibodies to a person before they are severely ill could potentially prevent worse outcomes.
The Columbia study suggests that the right mix of antibodies could be used as a therapeutic treatment for COVID-19. One way to produce them is to make them in a lab, although that may be difficult to do on a big scale. Monoclonal antibodies can be made in the laboratory by taking blood samples and taking the B cells. Those cells can then be introduced into mice, where they can produce antibodies. A research group at Vanderbilt is working on streamlining the isolation and discovery process.
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Antibodies as a treatment need to be tested for safety and efficacy like any other drug. “Once made, the antibodies would need to be tested in clinical trials to find out if they are safe and beneficial; prior experience suggests that they are likely to be beneficial as long as they are administered early enough in the infection,” says Eleanor Riley, who is a professor of immunology and infectious disease at University of Edinburgh and was not involved with the study.
But other aspects of our immune system may be more important than antibodies. “What is making all of this very difficult to predict is that we don’t know what part of our immune system correlates with protection [from SARS-CoV-2],” says John Swartzberg, a clinical professor emeritus of infectious diseases and vaccinology at the University of California, Berkeley School of Public Health, to Elemental. Specialized immune cells may turn out to be more important than antibodies, he notes. What gives experts hope that monoclonal antibodies will work are the studies that suggest antibodies from recovered patients can help people with severe COVID-19.
Part of the novelty with the two Nature studies is that they have identified a slew of antibodies that could be used together as a treatment. “We specifically isolated very potent antibodies that can be mass produced and then administered,” Ho tells The Guardian. “We would assume that these could be used to prevent or treat Sars-Cov-2. We’d be looking to treat early in the course of infection, particularly those at risk of developing severe disease such as the elderly and those with underlying illness.”
And while other groups have started manufacturing antibodies to use as treatment, they have typically only included a few types of antibodies, and making them on a large scale has remained a hurdle.
Regeneron begins human trials of a cocktail of two monoclonal antibodies that neutralize #SARSCoV2 and could treat or even prevent #COVID19. An especially promising type of drug candidate, but hard to manufacture at massive scale. https://t.co/pUB3o08KfC https://t.co/wX99ytR8dO https://t.co/S4rjkkG1f6
— David R. Liu (@davidrliu) June 11, 2020
Another factor to consider is the cost.
“However, these drugs do tend to be rather expensive and thus are likely to be reserved for treatment of severely ill patients or prevention of COVID-19 in high risk individuals,” says Riley. “Also, as the antibodies will wane over a period of days or weeks after treatment, they are not really suitable for long term prevention.”
This could mean that if used as a treatment for people at high risk of contracting SARS-CoV-2, they may need to get the treatment repeatedly to stay protected. A different research group working on synthetic antibodies says that they envision that treatment could involve one injection every two weeks or possibly once a month.
The more the merrier
The National Institutes of Health (NIH) are set to start a “flurry” of trials for coronavirus treatments. There are still aspects about the antibodies and how they work that we don’t fully understand yet.
“Some people who’ve had this have not had high antibody titers or have had low antibody titers,” says Anna Durbin, a vaccine researcher at Johns Hopkins University, to STAT. “We still don’t know what’s going to happen to them if they’re re-exposed.”
There could be advantages to using a mix of antibodies, especially if we end up fighting the coronavirus for years to come. “Using a cocktail of different antibodies that are directed to different sites in spike will help prevent the virus from becoming resistant to the treatment,” Ho said to The Guardian.
And it may be important to pursue various methods of treatments as well as multiple vaccine candidates because the coronavirus pandemic is ongoing. “In my opinion, the more antibodies the better, as scaling up antibodies, although standard, still requires time,” says Sachdev Sidhu at the University of Toronto who was not involved with the study and is planning to test neutralizing antibodies in clinical trials according to The Guardian. “Having multiple options will be good to ensure as many patients as possible can receive the therapies.”
For up-to-date information about COVID-19, check the websites of the Centers for Disease Control and Prevention and the World Health Organization. For updated global case counts, check this page maintained by Johns Hopkins University.
You can follow Chia-Yi Hou on Twitter.
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