Since the start of the COVID-19 pandemic, researchers have been working 24 hours to find an effective treatment. The first medicine it promises is dexamethasone, a cheap and widely available steroid. A large clinical trial conducted by the University of Oxford showed that the drug reduced the risk of death for COVID-19 patients in ventilators by a third, and by a fifth for those with oxygen.
Peter Horby, the trial’s principal investigator, described the results as a “breakthrough.” However, dexamethasone is not a panacea. Its beneficial effects are limited to critical patients with COVID-19 who need respiratory support. It has less impact on those with milder forms of the disease.
What is encouraging about dexamethasone is that it provides a proof of concept for future therapies. The drug works by blocking the overactive immune response triggered by SARS-CoV-2, the coronavirus that causes COVID-19. This can cause excessive inflammation, a complication often much more damaging than the virus itself.
Dexamethasone is just one of several anti-inflammatory drugs that are being investigated as a potential treatment for COVID-19. A large proportion of these drugs, many of which have appeared in recent years, are monoclonal antibody (mAb) drugs. These medicines contain antibodies – Y-shaped proteins produced by the immune system to fight foreign substances, such as bacteria and viruses. In the case of anti-inflammatory drugs, the antibodies are designed to block overactive cytokines, small proteins that regulate the inflammatory response.
Antibodies have been used to fight disease since the last decade of the 19th century, when it was discovered that the serum of animals that had survived diphtheria and tetanus conferred immunity in animals without prior exposure to such diseases and could cure diseases. This form of treatment, known as serum therapy, was so successful that it was the mainstay of infectious disease treatment until the emergence of antibiotics.
For much of the 20th century, the only source of antibodies were those that could be obtained from serum drawn from the blood of previously immunized animals. This, however, was a slow and expensive process, impossible to standardize.
The situation only changed after a breakthrough made at the Molecular Biology Laboratory, Cambridge, England, by César Milstein, an Argentine immunologist, and Georges Köhler, a German biologist. In 1975 they published a technique to produce unlimited amounts of antibodies identical to a specific target.
The method involves creating a hybrid cell line, known as a hybridoma, by fusing a short-lived antibody-producing B cell, a type of white blood cell, collected from the spleen of an animal immunized with an immortal cancer cell line. Maintained in a medium, the hybridoma can generate large amounts of what is known as “monoclonal antibodies”. The term “monoclonal” denotes the fact that the antibodies are all identical and clones of a single stem cell.
Awarded the Nobel Prize in 1984, the invention of Milstein and Köhler was soon used to treat people. The first mAb medication was licensed in 1986. Since then, more than 80 mAb medications have been licensed in the United States and Europe. They now account for a third of all new medicines introduced worldwide. Most of these are directed at cancer and autoimmune disorders, such as rheumatoid arthritis and multiple sclerosis.
Despite their success, little attention has been paid to the potential of mAb medications to treat COVID-19. This is somewhat surprising given its solid track record for treating immune disorders. Also, they are much faster to develop than the vaccines and antiviral medications that are currently in the limelight.
Part of the explanation may lie in the fact that so far only three mAb drugs have been licensed for infectious diseases. Slow progress in this area is due to the dominance of antibiotics, which are cheap to manufacture and easy to take. However, due to increased resistance to antibiotics, attitudes have recently begun to shift towards the development of mAb drugs to treat infectious diseases.
In the past, mAb medications were considered unsuitable for infectious diseases because they are so expensive to manufacture. But advances in recent years have helped reduce its cost.
Another obstacle is the fact that mAb medications must be administered intravenously. But this is not a problem for seriously ill COVID-19 patients who are already receiving intravenous infusions in intensive care.
Several mAb medications already approved for other conditions are now being tested for COVID-19. They include medications used to treat rheumatoid arthritis and other inflammatory conditions. Among them is infliximab, which made history in the 1990s by nullifying the conventional view that a mAb drug would never be successful as a treatment for inflammatory disorders.
Passive immunization
In addition to their potential to curb inflammation related to COVID-19, mAbs could help in another way. They could be used to protect people at high risk of exposure to infection, such as healthcare workers and people with compromised immune systems, such as those receiving chemotherapy. Known as passive immunization, this type of preventive treatment has been used for centuries.
The mAbs used for passive immunization are very different from those used to treat the inflammatory components of COVID-19. It involves the use of mAbs specifically directed against the SARS-CoV-2 virus. These mAbs have a couple of advantages over vaccines: They are much faster to develop and provide immunity in a matter of minutes. The downside is that protection only lasts a short time, usually months.
Monoclonal antibody drugs proved successful for passive immunization during the Ebola virus outbreak in West Africa between 2013 and 2016. Several teams around the world are now creating anti-SARS-CoV-2 mAbs for passive immunization. The former are expected to enter clinical trials next month. If they are successful, they will be useful in the absence of a vaccine.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Lara Marks received funding from the UK Medical Research Council and the Trust Fund for Medicine and Biotechnology Education (UK Registered Charity Number 1165469).
