Monoclonal Antibodies Could Help Fight Against Coronavirus

(Posted on Friday, April 24, 2020)

A group of Chinese scientists report the isolation of two human monoclonal antibodies with the potential to treat and to prevent SARS-CoV-2 infections, the causative agent of COVID-19. The work is described in a manuscript made available by Nature Cellular and Molecular Immunology. 

The two monoclonal antibodies block binding of the virus to the receptor preventing entry.

Such antibodies hold great promise for treatment as they are expected to prevent the virus spreading from cell to cell. The antibodies are also likely to protect those exposed, especially healthcare workers, from infection at least for a limited time. In both cases, the drugs would be administered intravenously.

No results demonstrating the activity of these potential drugs in animals or humans are reported. Nonetheless, previous experience with antivirus monoclonal antibodies of this type have been shown to be effective in treatment of both human and animal infections by viruses and other microorganisms. Monoclonal antibodies are among the most successful class of new drugs. Methods for manufacture and testing are well established. The FDA has approved more than 70 monoclonal antibodies for the treatment of human disease, including one for the treatment of respiratory syncytial virus a major cause of lower respiratory disease in children.

Several key questions remain open:

How soon will drugs be available? My guess, within three to four months for the first approvals.

• It may take several weeks to demonstrate effectiveness in animals.
• Human safety studies can be done with no more than 30 people in about a month. These drugs are generally known to be safe though more testing for safety will be required.
• Tests of the drugs’ effect in reducing the viral load in infected patients should take no longer than a month.
• Most time consuming will be large scale manufacturing of the drugs, once approved.

Some of these steps are undoubtedly already in process at this moment. China has the necessary skills and capacity to complete the research and testing and to manufacture at scale, as do many other countries. I know whereof I speak as I developed a similar drug for the treatment of and protection from anthrax infection and a monoclonal antibody for the treatment of Lupus.

Will the drugs work once patients become critically ill? The damage may already be too great to reverse. It is highly likely that the earlier the drug is administered post infection, the better.

If given to healthcare workers to protect them from infection, how long will the protection last? Best estimates for first generation antibody drugs is from 3 to 6 weeks. Follow on prophylactic treatments will be needed. Subsequent preparations may provide protection for up to four months.

There are several caveats.

• Coronaviruses, specifically those closely related to the SARS virus, are known to mutate to escape monoclonal antibody neutralization. The drugs may work for a while before the virus develops immunity. One way to counteract virus escape is to treat with two or more antibodies simultaneously.
• The drugs are relatively expensive to manufacture. The first generation must be grown in cell culture. It should be possible to develop future generations of drugs that act similarly but are far less expensive to produce.
• The antibodies were isolated from COVID-19 convalescent blood. Of the 26 convalescent patients studied, only three had the potential to block binding of the virus to its receptor, the ACE2 surface protein. Cells that produce antibodies were isolated from these three patients.
• The genes that produce the antibodies were isolated from these cells and used to create the two new drug candidates.

The work was completed by a team of scientists working in four different cities from across the length and breadth of China. While still in its early phases, the discovery is significant. There has been much talk in recent weeks about the use of convalescent serum and hyperimmune globulins—essentially, collecting blood from patients who have recovered from COVID-19 and giving the plasma to people who are sick. This discovery offers us the hope of a purer and potentially safer form of this type of treatment.

Note: This correspondence article has not been peer reviewed.

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Originally published on Forbes (April 23, 2020)