What’s the hoopla about monoclonal neutralizing antibody therapies?

Biology/Immunity Treatments

A: In short, neutralizing monoclonal antibodies are specialized proteins that can stop a particular virus from entering a cell and using it to make lots of copies of itself. Drug companies are developing a few different monoclonal antibodies intended to both prevent and treat COVID-19.

When a virus gets inside your body and is identified as a threat, your immune system fights back in part by producing antibodies. Antibodies are Y-shaped proteins. Each one has two sites that bind to a virus, located on the prong of the Y–what we call a variable region. Once your body has identified the shape of a particular virus, the immune system can make antibodies that are custom-fit to bind to it.

There are two types of antibodies: neutralizing antibodies prevent the virus from entering the cells. If viruses do not enter the cell, they cannot reproduce and spread. Non-neutralizing antibodies bind to the virus and tag it for other immune cells to destroy the virus.

Neutralizing antibodies work by stopping the virus from entering your cells. In this way, neutralizing antibodies prevent a virus from replicating and causing an infection in your body.
SARS-CoV-2, the virus that causes COVID-19, has a protein that fits a specific receptor on our cells (called ACE2). Think of this like a doorknob, and the virus is a hand. Neutralizing antibodies act like a giant oven mitt that would prevent the hand from grasping the doorknob.

You may have also heard about convalescent plasma donor therapy. The idea with this therapy is that the plasma from someone that has recently recovered from COVID-19 would have a lot of antibodies, which would bind the virus and clear it from the body.

Monoclonal antibodies work in a similar way. Companies have screened the plasma from people that have recently recovered from COVID-19 and chosen just a few neutralizing antibodies that are most effective in stopping the virus from entering cells. By mass producing one or two antibodies in a lab, companies can recreate an “off-the shelf” therapy rather than relying on donors to provide plasma.

There are at least two drug companies pursuing clinical trials with monoclonal antibodies: Eli Lilly and Regneron. Both of these companies are testing monoclonal neutralizing antibodies as a treatment for people who are already infected with COVID-19, and are also testing antibodies as a preventative treatment for high-risk individuals. One trial run by Regeneron and NIAID (part of the NIH) is focused on asymptomatic people that are household contacts of a COVID19+ person. Another preventative trial by El Lilly is focused on preventing infection for workers in assisted living facilities and nursing homes.

Monoclonal antibodies can fill the gap between a vaccine and an effective antiviral therapy. With a vaccine, the aim is to make the body produce antibodies that can neutralize the virus and prevent disease, hopefully for many years or for life. With antiviral therapies, the intent is to enhance viral clearance.

Monoclonal antibody therapies in theory could do both, but need to be given to patients at the right time. Because the antibodies are not being made by the body’s own immune system, these lab-manufactured antibodies are not renewed. They decrease over time once administered–usually within just a few weeks. The studies in progress now will determine if these treatments are effective as well as the dosing and timing needed to prevent and/or treat COVID19 infection.

For more on the clinical trials focused on prevention

Here’s a helpful basic overview of how antibodies work on Youtube (safe for kids)

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