ADE

Antibody-dependent Enhancement (ADE)…

A major goal of antibodies is to bind to the pathogen and prevent it from infecting, or entering, a cell. Antibodies that prevent entry into cells are called neutralizing antibodies. Many vaccines work by inducing neutralizing antibodies. However, not all antibody responses are created equal. Sometimes antibodies do not prevent cell entry and, on rare occasions, they may actually increase the ability of a virus to enter cells and cause a worsening of disease through something called antibody-dependent enhancement (ADE).” (CHOP has a fantastic layman explanation of ADE, link below).

A classic example of ADE was a vaccine made for dengue fever in 2016. The vaccine was given to 800,000 children in the Philippines. 14 vaccinated children died after encountering dengue virus in the community. Since, this vaccine has not been used for children under 9 years of age. In the 1960’s, we also saw ADE with a RSV vaccine and an early version of the measles vaccine. Trials for the RSV vaccine were immediately stopped and the vaccine was never distributed. The measles vaccine was fixed and now does NOT induce ADE.

Now in terms of COVID19…

Neither COVID-19 disease nor the new COVID-19 vaccines have shown evidence of causing ADE.

There were early concerns that COVID19 could induce ADE given a few conflicting animal studies. 2 animal studies showed the potential for ADE, while 3 animal studies did not show ADE. It’s clear that ADE is highly dependent on the type of vaccine. The 2 animal studies that showed potential were NOT testing mRNA vaccines (which gives you a small piece of an antibody, rather than the whole antibody). Vaccines with a high theoretical risk of inducing ADE are inactivated viral vaccines. However, it’s encouraging that a recent animal study of an inactivated COVID19 vaccine elicited strong neutralizing antibodies.

Nonetheless, this is why Phase II and Phase III are so crucial in clinical trials. We need to test enough people to ensure that things like this don’t come up. The trials are designed to find potential problems like ADE. And, there has been no evidence of ADE in the trials authorized for emergency use. If there was evidence of ADE, these vaccines would have never made it through and would have been quickly yanked from distribution.

Love, YLE

PS There is/was a PubMed nature article circulating stating the contrary. However, the authors did not state their reasons as to WHY they are concerned about it. They just say they are. Which is not helpful. Also, keep in mind that any article can be uploaded to PubMed. If it’s on PubMed, it doesn’t necessarily mean it’s been peer-reviewed… an important distinction.

Here are some great sources:

A science heavy explanation: https://www.nature.com/articles/s41564-020-00789-5

A good layman explanation: https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-safety/antibody-dependent-enhancement-and-vaccines