Now that we’re several years removed from the pandemic, I imagine no one wants to hear about COVID-19 vaccines anymore. However, there was a nice result published this month that solves a nagging problem from that time.
In contrast to the conspiracy theories, it is a nice example of how scientists try to assess vaccines honestly, then improve them incrementally.
By the end of 2021, there were two broad types of COVID-19 vaccines widely available in the U.S. The difference between the two was how each vaccine delivered the genetic information for the COVID-19 spike to the human body.
The first type used mRNA; the second, more traditional, type used parts of a common virus to deliver the genetic information. One of those traditional ones, produced by Johnson & Johnson, specifically used an adenovirus.
The adenovirus vaccine, unfortunately, had a rare side effect, called VITT. The most important symptom was the development of blood clotting difficulties.
By the end of 2021, about 54 cases had been identified in the U.S. There were nine fatalities. For perspective, about 460,000 people died in the U.S. in 2021 as a result of COVID-19.
The recommendation for or against the adenovirus-based vaccine was based on the relative risk of COVID-19 vs. VITT, along with the other vaccine options. Because of VITT and being able to use the mRNA vaccines, the Johnson & Johnson vaccine was abandoned in 2021.
We now know exactly why the adenovirus vaccine caused that reaction. The problem was solved by scientists at Flinders University (Australia), the University of Greifswald (Germany) and McMaster University (Canada). They published their results in February in the New England Journal of Medicine.
The condition is rare because, as the scientists showed, several things must go wrong.
One key clue came when the scientists analyzed 21 patients with VITT. All the patients had an unexpected antibody that attacks a protein called PF4. PF4 plays a role in blood clotting, so it made sense this was related.
The scientists had also identified the same antibodies in patients who had the same symptoms but had been infected by the wild version of the adenovirus. This evidence further cemented the VITT connection to the adenovirus.
The scientists analyzed the antibodies in more detail by determining the antibody’s exact chain of amino acids.
For this antibody, the VITT patients were different in two ways. First, at position 50 the antibodies had an unusual mutation resulting in aspartic acid instead of the more common tyrosine. Second, at position 31 the antibodies had another mutation resulting in glutamic acid or aspartic acid instead of lysine.
The important thing is not that these amino acid names are familiar (they were not to me), but that it shows the scientists made very specific discoveries, not just general arguments.
Both changes result in negative charges at those locations. Those negative charges then make the antibodies an especially good fit in attaching to PF4, which has positive charges at complementary positions.
After attaching to several PF4 proteins, the antibodies collect at platelets, which in turn release more PF4 proteins, leading to a chain reaction.
The platelets become distracted and cannot respond to their traditional blood clotting functions.
The scientists confirmed this chain of reasoning by several experiments in mice.
First, they injected mice with the VITT-related antibodies and obtained the same negative reaction. Second, they “fixed” the antibodies by changing the amino acid at position 31, injected the antibodies into mice and obtained a much more mild negative reaction.
This work is still critical for vaccine development. The adenovirus approach has a lot of advantages.
First, these vaccines are stable. They can be kept in standard refrigerators, for example. They are also quite good at eliciting an immune reaction, which is the point of a vaccine.
Lastly, they are relatively quick and cheap to produce, which makes them especially attractive when designing vaccines to be used in low-income countries or in the early stages of a new pandemic.
As a result of these advantages, adenovirus-based vaccines are still being developed for Ebola, malaria, tuberculosis and meningitis.
Now that we understand the exact process, down to the molecule, that leads to VITT, it may be possible to alter the part of the adenovirus to prevent the harmful chain reaction.
This is what scientific progress looks like, one important step at a time. No conspiracies and an honest, public evaluation of what we know.
Christer Watson of Fort Wayne holds a doctorate in astronomy and writes about the applications of science in everyday life.