US FDA is investigating the vaccine design behind COVID-19 shots related to blood clots

By Julie Steenhuysen and Kate Kelland

CHICAGO / LONDON (Reuters) – With two COVID-19 vaccines now under investigation for possible links to very rare cases of blood clots in the brain, US government scientists are focusing on whether the specific technology behind the injections can contribute to the risk.

In Europe, health regulators said last week that there was a possible link between the AstraZeneca Plc vaccine and 169 cases of a rare brain blood clot known as cerebral venous sinus thrombosis (CVST), accompanied by a low platelet count, out of a total of 34 million shots. managed in the European Economic Area.

The U.S. Food and Drug Administration on Tuesday recommended a temporary halt to use of the Johnson & Johnson vaccine following reports of six cases of CVST in women under age 50 among about 7 million people who received the injection in the United States.

Both vaccines are based on a new technology that uses adenoviruses, which cause colds, that have been modified to make them essentially harmless. The viruses are used as vectors to convey instructions for human cells to make proteins found on the surface of the coronavirus, preparing the immune system to make antibodies that fight the actual virus.

Scientists are working to find the possible mechanism that could explain the blood clots. A leading hypothesis appears to be that the vaccines trigger a rare immune response that could be related to these viral vectors, FDA officials said at a briefing Tuesday.

The US agency will analyze data from clinical trials of various vaccines using these viral vectors, including J & J’s Ebola vaccine, to look for clues.

None of the previous viral vector vaccines have been administered at the AstraZeneca and J&J COVID-19 injections scale, which might explain why a potential link with blood clots only emerged during these massive vaccination programs.

The technology has also been used in coronavirus vaccines developed in China and Russia.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, was reluctant to call the blood clot issues a “class effect” shared by all adenovirus vector vaccines, but he sees clear similarity in the cases.

“It is clearly already clear to us that what we are seeing with the Janssen (J&J) vaccine is very similar to what we are seeing with the AstraZeneca vaccine,” said Marks. “We can’t make a general statement yet, but they clearly belong to the same general class of viral vectors.”


In Europe, scientists are investigating a number of hypotheses, including a broader look at how the SARS-CoV-2 virus itself affects blood clotting.

A team in the Netherlands plans to conduct laboratory studies that expose specific types of cells and tissues to the vaccines and monitor how they respond. They will also investigate whether any risks can be further reduced by lowering the vaccine dose.

“There are many hypotheses, and some may play a role,” says Eric van Gorp, virologist at the Erasmus Medical Center in Rotterdam. “We are at the beginning, and – as it is in research – we may be able to find the clue right away, or it may be step-by-step.”

Other scientists were struck by the parallel between J&J and AstraZeneca’s images.

Danny Altmann, a professor of immunology at Imperial College London, said the similar blood clotting events associated with both “are clearly remarkable for defining the mechanism.” There are no signs of such problems with the vaccines made by BioNTech SE with Pfizer Inc or Moderna Inc using any other technology.

“It would be interesting to know more about Sputnik V – also a similar adenovirus vaccine,” said Altmann. The Russian vaccine developed by the Gamaleya Institute in Moscow uses two different human cold viruses – including the Ad26 virus in the J&J image.

The issue could also affect CanSino Biological’s adenovirus vector vaccine of China, experts said.

Investigating whether there is a common link with adenoviruses is “reasonable speculation, and it is a line of research and research. But that doesn’t mean it’s proven,” said John Moore, a professor of microbiology and immunology at Weill Cornell Medical. College in New York.

Moore, who attended an informal White House briefing with other scientists on Tuesday, said the FDA and the U.S. Centers for Disease Control and Prevention are working closely with health officials in Europe to determine whether the syndromes related to the AstraZeneca J&J vaccines the same.

An important indication may be that the reported events usually occur about 13 days after the injection, which is the time period during which antibodies can be expected.

“This is speculation, but the timing of something that happens on average after about 13 days indicates an immune response to some component of the vaccine,” said Moore.

These types of studies can take years. But like the vaccines themselves that were produced in record time, Moore believes so much effort will be put into the research that it will likely be resolved within weeks.

“It’s so obviously important,” he said.

(Reporting by Julie Steenhuysen and Kate Kelland; additional reporting by Michael Erman Maplewood, NJ; edited by Michele Gershberg and Bill Berkrot)