BY FRANCISCO DELGADO – SEPTEMBER 25, 2020
As the coronavirus (SARS-CoV-2) continues to wreak havoc throughout the world, scientists have been working diligently to come up with a solution to this daunting pandemic. Hopes remain high for a vaccine, but a safe and effective one may not come soon enough to prevent more people from being infected.
In the meantime, researchers are looking furiously for alternative forms of treatment that can help those who have already been infected. We know so far that steroids and a new antiviral medication called Remdesivir can provide some relief by acting directly on the virus and preventing replication, but better medications are needed, and soon.
We can also find solutions by learning how the immune system protects us against viral infections. Novel biomedical solutions involve B cells: Convalescent plasma therapy and monoclonal antibodies. By mimicking the immune system’s operation, biomedical researchers are making significant progress toward this end, highlighting the elegant and sophisticated design of the immune system.
When a virus or another microorganism enters the body, it is initially captured by sentinel cells in our immune system. These cells break the microorganism into many fragments and “present” these fragments to special cells called B cells. The B cells that “recognize” the fragments will be recruited in the fight against the microorganism. The cells will replicate themselves in high numbers and become factories that produce proteins called antibodies whose goal is to neutralize the microorganism and protect the body from further harm. The population of B cells is a clone of the original one that recognized the fragments presented by the sentinel cells and the antibodies are highly specific in targeting the particular infecting microorganism.
Convalescent Plasma Therapy
When a person is in the recovery stage from a viral infection, these B cells produce a significant amount of specific antibodies against the virus circulating in their blood. This principle is the basis for convalescent plasma therapy, in which the blood from a person who has recovered from a viral infection is harvested and the plasma or liquid portion of the blood that contains these antibodies is separated. This plasma is then transfused to a sick person with the hope that it contains enough antibodies to fight the virus and let the person recover more rapidly.
Even though the principles for convalescent plasma therapy are straightforward, the plasma may not have enough neutralizing antibodies to help the sick person who is receiving it. If this is the case, the benefit may be minimal. One of the solutions for this problem is to “pool” many donors and prepare a mixture of plasma from different donors in the hope that one may have enough neutralizing antibodies to fight the infection. Another solution is to screen the plasma for those neutralizing antibodies and use the plasma units that have a high number of antibodies against a pathogen.
In a second research effort, scientists have sought to take the guesswork out of the process of harvesting convalescent plasma by employing a new technique in the medical field called monoclonal antibodies. Monoclonal antibodies try to mimic the way in which the B cells protect us against viral infections. These antibodies are proteins designed to attach to specific three-dimensional molecules. That interaction can result in the modification of a cell function or, in the case of infectious diseases, block a pathogen from entering a cell.
The use of monoclonal antibodies is relatively new. The first monoclonal antibody was licensed in 1986.1 Today there are over 75 FDA-licensed monoclonal antibodies that researchers use to treat cancer, chronic inflammatory diseases, cardiovascular diseases, and to aid in transplantation. However, only a handful of them are available for the treatment of infectious diseases. One of the most recent successful such applications involved treatment of Ebola virus.2
There are several ways to manufacture monoclonal antibodies, but all are complex and expensive. Some of them use human tissue and some use transgenic mice.3 Once biomedical researchers obtain the desired antibody (or mixture of antibodies), it proceeds through clinical trials to evaluate its efficacy as a treatment for a disease. The process to produce an effective monoclonal antibody is long and can take months to years. Nevertheless, this solution has materialized by studying the human immune system in exquisite detail.
The COVID-19 Challenge
Coronaviruses have a very distinct protein on their surface that resembles a crown. It is this protein (SPIKE protein) that gives the virus its name (corona = crown). The interaction of this protein with the ACE2 protein on the surface of a human cell allows the virus to invade the cell and start its replication cycle. During the first months of the pandemic, researchers studied the SPIKE protein in great depth and they have now developed monoclonal antibodies against this protein.4 As of today, a few companies have moved to the testing phase for some of these antibodies in clinical trials. However, results may not be available until late 2020. Nevertheless, some people believe that researchers will produce monoclonal antibodies before we have a vaccine against SARS-CoV-2.5
The Case for Design
The coronavirus pandemic has sparked a massive hunt for solutions that can help decrease the virus’s global impact. The amount of resources and the number of people involved in the development of novel therapies is astounding.
It is remarkable to think that with all the accumulated knowledge in the world and with a massive amount of resources behind this research, it will take us many months to accomplish what the immune system can do in just a few days. The complexity and efficiency with which our bodies run this process speak loudly about the exquisite design of our immune system. As the psalmist writes, we truly are “fearfully and wonderfully made.”
- Justin K. H. Liu, “The History of Monoclonal Antibody Development—Progress, Remaining Challenges and Future Innovations,” Annals of Medicine and Surgery 3, no. 4 (December 2014): 113–16, .
- Sabue Mulangu et al., “A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics,” New England Journal of Medicine 381 (December 12, 2019): 2293–2303,
- Laura M. Walker and Dennis R. Burton, “Passive Immunotherapy of Viral Infections: ‘Super Antibodies’ Enter the Fray,” Nature Reviews Immunology 18 (January 30, 2018): 297–308,
- Xiaolong Tian et al., “Potent Binding of 2019 Novel Coronavirus Spike Protein by a SARS Coronavirus-Specific Human Monoclonal Antibody,” Emerging Microbes and Infections, vol. 9 no. 1 (February 17, 2020): 382–85,
- Jon Cohen, “Antibodies May Curb Pandemic before Vaccines,” Science 369, no. 6505 (August 14, 2020): 752–53, doi:10.1126/science.369.6505.752.