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Researchers pinpoint cause of rare but life-threatening blood clots after adenovirus-based COVID vaccination
Mary Van Beusekom, MS
59 minutes ago.
COVID-19 Scientists say they have identified a mutated autoantibody gene as the mechanism behind rare but serious abnormal blood clotting after adenovirus-based COVID-19 vaccination, a discovery that they say will allow vaccine developers to avert the disorder by adjusting the adenovirus protein in the vaccines while still preserving their efficacy.
For the study, published yesterday in the New England Journal of Medicine, researchers in Australia, Canada, and Europe used mass spectroscopy and molecular analysis to delve into why, at the COVID-19 pandemic peak in 2021, a small number of people developed vaccine-induced immune thrombocytopenia and thrombosis (VITT) after receiving adenovirus vector-based vaccines or experiencing an adenovirus infection.
Effect limited to adenovirus COVID vaccines
VITT occurred in roughly one of 200,000 people after receipt of the Oxford-AstraZeneca COVID-19 vaccine in Europe and Australia or the Johnson & Johnson (J&J) vaccine in the United States.
Adenoviruses are common viruses that cause mild or moderate diseases such as the common cold and bronchitis. These vaccines used an adenovirus to insert a gene for SARS-CoV-2’s spike protein into recipients’ cells.
After VITT was linked to adenovirus-based vaccines, many European countries either limited the use of the AstraZeneca vaccine or dropped it completely, and the United States abandoned the J&J vaccine. mRNA-based COVID-19 vaccines such as those from Moderna or Pfizer/BioNTech were much more commonly used in the United States and under different brand names in many other countries.
A new syndrome, VITT is characterized by thrombosis, or the formation of dangerous blood clots in the veins or arteries, often in the brain or abdomen. It is accompanied by immune thrombocytopenia, an autoimmune disorder that depletes platelets in the blood, leading to uncontrolled bleeding. Symptoms can include severe headache, changes in vision, abdominal and back pain, vomiting, shortness of breath, easy bruising or bleeding, and leg pain or swelling.
‘A brilliant piece of molecular sleuthing’
The probe led to detection of a mutation in a person’s antibody-producing B cells that causes the immune system to mistake a normal adenovirus protein for human blood protein platelet factor 4 (PF4), prompting the production of an antibody that triggers blood clotting.
It is a brilliant piece of molecular sleuthing, the culmination of a body of work that unravels the genetic and structural basis for how a normal immune response to a virus protein leads to pathogenic autoimmunity.
James McCluskey, MD
The researchers say that VITT patients had likely previously been infected with an adenovirus, which primed their B cells to recognize the adenovirus protein.
The finding can also improve the safety of adenovirus-based vaccines against other diseases such as Ebola. “By modifying or removing this specific adenovirus protein, future vaccines can avoid this extremely rare reaction while continuing to provide strong protection against disease,” lead author Jing Jing Wang, PhD, of Flinders University in Australia, said in a university news release.
“A novel aspect of the paper was our use of powerful mass spectrometry sequencing to identify molecular mimicry between the adenovirus vector protein and the PF4 culprit target,” she added. “This was the missing link that explains how a normal immune response can, in very rare cases, become harmful.”
Coauthor James McCluskey, MD, of the University of Melbourne in Australia, hailed the study as a major scientific achievement: “It is a brilliant piece of molecular sleuthing, the culmination of a body of work that unravels the genetic and structural basis for how a normal immune response to a virus protein leads to pathogenic autoimmunity.”
Researchers pinpoint cause of rare but life-threatening blood clots after adenovirus-based COVID vaccination
Mary Van Beusekom, MS
59 minutes ago.
COVID-19 Scientists say they have identified a mutated autoantibody gene as the mechanism behind rare but serious abnormal blood clotting after adenovirus-based COVID-19 vaccination, a discovery that they say will allow vaccine developers to avert the disorder by adjusting the adenovirus protein in the vaccines while still preserving their efficacy.
For the study, published yesterday in the New England Journal of Medicine, researchers in Australia, Canada, and Europe used mass spectroscopy and molecular analysis to delve into why, at the COVID-19 pandemic peak in 2021, a small number of people developed vaccine-induced immune thrombocytopenia and thrombosis (VITT) after receiving adenovirus vector-based vaccines or experiencing an adenovirus infection.
Effect limited to adenovirus COVID vaccines
VITT occurred in roughly one of 200,000 people after receipt of the Oxford-AstraZeneca COVID-19 vaccine in Europe and Australia or the Johnson & Johnson (J&J) vaccine in the United States.
Adenoviruses are common viruses that cause mild or moderate diseases such as the common cold and bronchitis. These vaccines used an adenovirus to insert a gene for SARS-CoV-2’s spike protein into recipients’ cells.
After VITT was linked to adenovirus-based vaccines, many European countries either limited the use of the AstraZeneca vaccine or dropped it completely, and the United States abandoned the J&J vaccine. mRNA-based COVID-19 vaccines such as those from Moderna or Pfizer/BioNTech were much more commonly used in the United States and under different brand names in many other countries.
A new syndrome, VITT is characterized by thrombosis, or the formation of dangerous blood clots in the veins or arteries, often in the brain or abdomen. It is accompanied by immune thrombocytopenia, an autoimmune disorder that depletes platelets in the blood, leading to uncontrolled bleeding. Symptoms can include severe headache, changes in vision, abdominal and back pain, vomiting, shortness of breath, easy bruising or bleeding, and leg pain or swelling.
‘A brilliant piece of molecular sleuthing’
The probe led to detection of a mutation in a person’s antibody-producing B cells that causes the immune system to mistake a normal adenovirus protein for human blood protein platelet factor 4 (PF4), prompting the production of an antibody that triggers blood clotting.
It is a brilliant piece of molecular sleuthing, the culmination of a body of work that unravels the genetic and structural basis for how a normal immune response to a virus protein leads to pathogenic autoimmunity.
James McCluskey, MD
The researchers say that VITT patients had likely previously been infected with an adenovirus, which primed their B cells to recognize the adenovirus protein.
The finding can also improve the safety of adenovirus-based vaccines against other diseases such as Ebola. “By modifying or removing this specific adenovirus protein, future vaccines can avoid this extremely rare reaction while continuing to provide strong protection against disease,” lead author Jing Jing Wang, PhD, of Flinders University in Australia, said in a university news release.
“A novel aspect of the paper was our use of powerful mass spectrometry sequencing to identify molecular mimicry between the adenovirus vector protein and the PF4 culprit target,” she added. “This was the missing link that explains how a normal immune response can, in very rare cases, become harmful.”
Coauthor James McCluskey, MD, of the University of Melbourne in Australia, hailed the study as a major scientific achievement: “It is a brilliant piece of molecular sleuthing, the culmination of a body of work that unravels the genetic and structural basis for how a normal immune response to a virus protein leads to pathogenic autoimmunity.”