What is Antibody Dependent Enhancement (ADE) and why is it a concern?

What is Antibody Dependent Enhancement (ADE) and why is it a concern?

Antibody Dependent Enhancement (ADE) is not a good thing, even though it may sound positive. “Pathogenic Priming” and “Immune Enhancement” are also terms used to describe this situation. Here are some published links for your reference-

https://www.nature.com/articles/s41564-020-00789-5.pdf

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7142689/

This unwelcome situation occurs when one develops antibodies that bind to a pathogen, but do not actually kill it. Hence, they are called ‘binding or non-sterilizing antibodies’. In contrast, antibodies that destroy the pathogen are called ‘neutralizing or sterilizing antibodies’. Non-sterilizing antibodies are not only ineffective at protecting us from an infection, but they may place us at risk of more severe illness should ADE be stimulated.

To offer some background, the body has two components to its immune system. The innate immune system uses nonspecific mechanisms to prevent a pathogen from entering the body or spreading, including things like inflammation, stomach acid, and mucus. The acquired immune system, on the other hand, creates a response that is much more specific to the pathogenand more aggressive. It needs to be trained so that it can develop antibodies to the specific invading pathogen and other mechanisms to remember it. This is the theory behind vaccines.  Vaccines stimulate the acquired immune system to create antibodies and memory to an inactivated or weakened (will not make you sick) pathogen or its parts. Many of our traditional vaccines created sterilizing antibodies.  These antibodies successfully prevent the pathogen from replicating and spreading to others. This is why they were successful in eradicating or controlling diseases such as small pox. The SARS-CoV-2 vaccines are no longer sterilizing vaccines. Not only is the infected person at risk of becoming sick with COVID-19, their response may be worsened by ADE. When a non-sterilizing antibody binds to the virus, it may actually help the virus enter one’s immune cells where it can replicate and destroy them, or it may attract other cells that produce an uncontrolled inflammatory response that can worsen the person’s illness or may be fatal. Scientists and clinicians will need to closely monitor for any evidence of ADE in the immunized population.

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