Where Do The Thrombi Caused By AstraZeneca And Janssen Vaccines Come From?

The United States decided tostop vaccination with Janssen on Tuesday. Now, the source of a series of thrombi very similar to those associated with AstraZeneca's vaccine is to be investigated.

Shortly thereafter, the company announced a delay in the imminent launch of its European dose while thrombosis in patients already vaccinated with Janssen are being investigated.

Why is it happening with AstraZeneca and Janssen?

The truth is that AstraZeneca's vaccine and Johnson & Johnson's single-dose vaccine are based on very similar technology. Both use adenovirus as a vehicle to activate the immune response. This component appears to be responsible for thrombosis, according to experts who have explained the strongest hypothesis so far about the strange cases of thrombi with low platelet levels.

Adenovirus-based doses have been under investigation for years. However, they have never been used on a massive scale in humans.

Although there is one approved against Ebola, the only one frequently used is rabies for animals.

AstraZeneca's thrombus research has genetic implications for this type of vaccine to which belong, in addition to Janssen's, the Russian vaccine Sputnik and the Chinese one, CanSino. 

All of them have this basic element in common, which serves as a platform for vaccine development.

All this would explain why so far there have been no similar thrombosis problems with the Pfizer and Moderna vaccines, which are based on a different technology, that of messenger RNA.

A powerful research

Several weeks ago, the team of German hematologists led by Andreas Greinacher pointed to a strange autoimmune reaction as the cause of the investigated thrombi. 

Somehow, the vaccine caused an activation of antibodies that disturbed the platelets, attacked them, and as a consequence led to thrombus formation.

In a new paper, published in The New England Journal of Medicine, Greinacher and colleagues detailed how they believe this reaction happens and noted that it would be directly related to adenovirus. 

These viruses are essentially DNA that needs to enter a cell to leave its genetic message. In each dose of AstraZeneca's vaccine, there are 50,000 virus particles, and instead of entering cells, some of them are attracted to a protein essential for blood clotting, called platelet factor 4, better known as PF4. 

Hematologist Ramón Lecumberri explains what this mechanism consists of, which is quite similar to an uncommon side effect of heparin called HIT and which triggers antibodies against the PF4 protein.

"This protein has a positive charge, so any substance with a high negative charge, such as heparin or adenovirus DNA, will tend to bind to that protein," says this expert.

One of the experts in this type of thrombus who has investigated what happened with AstraZeneca, Theodore Warkentin, has stressed that the key may lie in free DNA. This means that it is some genetic fragment not contained in the adenovirus that may be benefiting this abnormal union with the human protein.

This association occurs in very few cases, but when it does occur, the organism no longer recognizes the PF4 protein. Since it is attached to the DNA of the virus, it becomes a foreign element against which antibodies are generated. 

Although the adenovirus used by AstraZeneca, Janssen or Sputnik are different, "the mechanism could be the same," warns Ramón Lecumberri.

Adenovirus vaccines

The adenovirus used by Janssen and AstraZeneca are common cold viruses that are genetically modified to introduce into the human body the coronavirus S protein, which is the one used by SARS-CoV-2 to infect human cells.

In this way, the immune system recognizes it and can activate the defenses against a real infection.

Now, the issue is to find out whether, in this process, there may be problems for some people in whom the adenovirus would also trigger this rare autoimmune reaction: thrombi, coagulation, and a drop in platelets.

"The problem is that not only do the platelets go down, but they also become activated and produce thrombi. These antibodies, when they bind to FP4, have the particularity of activating the platelets: they aggregate with each other and are also the ideal breeding ground for a cascade of coagulation to occur," this expert points out.

Despite all this, Lecumberri calls for calm. The fact is that an investigation is underway to determine whether there is a link between six new cases of thrombi, which occurred in the United States among the more than seven million people vaccinated, and the Janssen dose, as was previously done with AstraZeneca. 

[This is a translation of the original article "Ya se sabe de dónde pueden venir los trombos de AstraZeneca y Janssen" published in espanadiario.net]