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Are COVID-19 vaccines causing antibody-dependent enhancement?

This article was published on
May 25, 2021

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As of May 2021, there is no evidence to suggest that COVID-19 vaccines are leading to antibody-dependent enhancement.

As of May 2021, there is no evidence to suggest that COVID-19 vaccines are leading to antibody-dependent enhancement.

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What our experts say

Developing antibodies after a vaccine is normally an expected and positive thing. Antibodies (from vaccines or from recovering from a previous infection) are key to getting our immune systems to properly fight a virus.

Sometimes, after developing antibodies to a disease, our immune system can overreact the next time it gets exposed to the disease. This is a very rare phenomenon called antibody-dependent enhancement (ADE).

The antibodies involved in ADE don't help the body's immune response, but instead might even make things worse. ADE increases the chance that a person will develop severe symptoms of a disease when they are infected.

Antibodies that lead to ADE work like a "Trojan horse" by letting the virus into the cells and making the immune response overactive. They allow the virus to attach to our cells, causing inflammation and an enhanced immune system response.

So far there have been no verified reports of ADE occurring as a result of COVID-19 vaccines.

ADE has been seen in the past with virus and vaccine responses:

  • Dengue fever and its 2016 vaccine deployment in the Philippines
  • Respiratory syncytial virus (RSV) vaccine trials on children in the United States (U.S.) in 1967
  • A now-rejected vaccine developed for measles in the U.S. in the 1960s.

In the process of making COVID-19 vaccines, scientists developed vaccine strategies around avoiding ADE. These include:

  • Specifically targeting a SARS-CoV-2 protein that was the least likely to cause ADE in early vaccine design
  • Designing animal studies to search for ADE after vaccination
  • Evaluating human and clinical trial patients for the condition
  • Searching real world COVID-19 vaccine data for cases

Most COVID-19 vaccines target the spike protein in the virus in a defined way that is low risk. New vaccine technologies like mRNA are safer and designed in more scientifically targeted ways than older vaccines. Overwhelmingly, vaccinated people are showing protection against severe COVID-19 cases and hospitalizations. This would likely not happen if ADE were occurring, because it is an acute and very serious condition that would cause significant medical alarm.

Outside of vaccines, when COVID-19 patients were treated with plasma (which contained SARS-CoV-2 antibodies), more severe disease from ADE was never documented and likely did not occur.

To be sure, there is little information and some concern about "inactivated whole cell vaccines," like the ones developed by China in response to COVID-19. This kind of vaccine includes an ingredient called 'alum' that's meant to enhance immune responses to the vaccine. Alum was also used in the measles and RSV vaccines in the 1960s, which did lead to ADE. There have not been any ADE occurrences reported in clinical trial data from the Sinovac and Sinopharm vaccines that have been documented in peer-reviewed literature.

Context and background

It's important to distinguish that the COVID-19 virus does not cause us to produce antibodies. The human immune system does that as a reaction to the COVID-19 pathogen. Antibodies we produce after the COVID-19 vaccine help stop the virus from circulating and mutating further. Antibodies do not make variants stronger or more harmful.

Unvaccinated people are the major producers of viral variants, data suggests. Some of these variants can evade the antibodies in our systems that protect us against COVID-19. Thankfully, most vaccines are effective enough to fight off the majority of circulating variants.

Many posts on social media have been linked to topics such as ADE, in addition to other vaccine-related subjects. One such post references an inaccurate quote made by French virologist Luc Montagnier in a recent interview for a documentary called “Hold-Up.” In this clip, Montagnier said that after a person is vaccinated the virus is not actually killed or neutralized. Instead, the virus finds "another solution" in the form of variants. The virologist also allegedly stated, “You see it in each country; it’s the same: The curve of vaccinations is followed by the curve of deaths.”

Many experts in virology and epidemiology have noted that this claim is false. Mutations are part of the natural evolution of viruses and COVID-19 began mutating before vaccines were in the picture. Similarly, the variants of concern noted by the World Health Organization started to emerge before any vaccine campaigns began.

If vaccines did cause more variants, we would see cases and variants increase in tandem together in regions with high immunization rates. Data published from highly vaccinated populations has shown the contrary: a decrease in cases and fewer people for the virus to infect, making the virus unable to mutate more. Vaccines also help keep viral variants to a limited number, not a larger one.

Some online mistruths are based on historical information that compares previous viruses and vaccination designs to COVID-19. It's important to note that scientists deliberately designed their COVID-19 vaccines to prevent ADE from occurring. Evidence has shown their attempts have been successful. The most recently published data on COVID-19 immune response after vaccination have not indicated that ADE is occurring in immunized populations.

Available data suggests that unvaccinated people are the major producers of viral variants, some of which can evade antibodies. Most vaccines are effective enough to fight off the majority of antibodies that are now circulating.

Resources

  1. Comparing infectivity and virulence of emerging SARS-CoV-2 variants in Syrian hamsters (The Lancet)
  2. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies (Nature)
  3. Antibody-Dependent Enhancement and the Coronavirus Vaccines (Science Translational Medicine)
  4. COVID-19 Vaccines: Should We Fear ADE? (The Journal of Infectious Diseases)
  5. Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies (Frontiers in Immunology)
  6. The impact of COVID-19 vaccination campaigns accounting for antibody-dependent enhancement (PLOS One)
  7. Do the mRNA vaccines cause Antibody Dependent Enhancement (ADE) with COVID-19 disease? (Immunize BC)
  8. Antibody-dependent Enhancement (ADE) and Vaccines (Children's Hospital of Philadelphia)
  9. Antibody Dependent Enhancement and SARS-CoV-2 (Global Virus Network)
  10. ADE and Corona Vaccines (Davidson Institute of Science Education)
  11. Why ADE Hasn't Been a Problem With COVID Vaccines (MedPage Today)
  12. No, COVID-19 Vaccines Do Not Cause New Coronavirus Variants (healthline)

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