Dr. Amy Rogers
2 min readJan 19, 2022

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I said ask me if you want a technical explanation for why monoclonal antibodies fail. Someone asked. Here is my reply:

The immune system forms antibodies against “foreign” proteins that enter the body. We call the unwanted or alien thing an “antigen."

Antibodies grab onto the antigen by a careful, precise fit. So in general terms, for example, an antibody against peanut will not stick to a piece of coronavirus.

But while we might think of “peanut” or “coronavirus” antigen as one thing, it’s actually hundreds or thousands of different things that are available for antibodies to grab on.

I like to use the analogy of the blind men and an elephant, if you know that one. A group of blind men are placed in a room with an elephant and asked to describe the elephant. One touches the tusk and says elephants are hard and sharp like stone. One touches a leg and says elephants are stout and heavy like trees. One touches the trunk and ...

The elephant is the whole antigen, but different antibodies recognize different parts of it.

All the US COVID vaccines use some method to deliver the coronavirus “spike protein” as the antigen. A vaccinated person will produce a wide range of different antibodies against different parts of the spike protein. If a new variant of the coronavirus has mutations that change the spike protein, some of those antibodies will no longer recognize it, but some of them will. So our immune system has some redundancy that gives at least some protection against future variants.

Manufactured monoclonal antibodies, however, do not have variety—hence the name “mono”clonal. They are a pharmaceutical product based on just one specific antibody that sticks to just one part of the spike protein. Using the analogy, a vaccinated immune system can see the tusk, the tail, the leg, and the trunk; a monoclonal antibody product can only see one of those. If that one part is changed by a mutation in the virus, the monoclonal antibody therapy will not work. This is what has happened with some of the monoclonal products and the omicron variant.

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Dr. Amy Rogers

Amy Rogers, MD, PhD, is a Harvard-educated scientist, novelist, journalist, and educator. She blogs about coronavirus at AmyRogers.com