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Research


VERY RARE COVID VACCINE-RELATED BLOOD CLOTS SHARE GENES WITH CONDITION LINKED TO
COMMON COLD

By Helen FloershMay 17, 2024 1:08am
COVID-19blood clotsvaccinesAstraZeneca

With regards to the AstraZeneca and Johnson & Johnson vaccines, the findings
concretely implicate the adenovirus as the culprit behind rare cases of
vaccine-induced immune thrombocytopenia and thrombosis. (Kunal
Mahto/iStock/Getty Images Plus/Getty Images)

The rare, deadly blood clots triggered by an autoimmune response to the COVID-19
vaccines from Johnson & Johnson and AstraZeneca seem to be caused by a gene
that’s also responsible for an unusual but almost identical reaction to the
virus that causes the common cold. The findings could have implications for
future vaccines. 

In a letter published May 15 in The New England Journal of Medicine, an
international team of scientists explained that people who carry certain
variants of a gene called IGLV3-21*02 are predisposed to developing both
vaccine-induced immune thrombocytopenia and thrombosis (VITT) and the same type
of reaction after infection with the adenovirus. Both the J&J and AstraZeneca
vaccines are delivered to the body in adenovirus vectors, which explains why the
etiology of the conditions is the same. 







“Our findings have the important clinical implication that lessons learned from
VITT are applicable to rare cases of blood clotting after adenovirus infections,
as well as having implications for vaccine development," Tom Gordon, M.D.,
Ph.D., of Flinders University, who led the co-study, said in a press
release. Theodore Warkentin, M.D. from McMaster University in Canada and Andreas
Greinacher, M.D., from Greifswald University in Germany also led the work. 





AstraZeneca’s vaccine, Vaxzevria, was dogged by reports of VITT not long after
the shot rolled out in Europe. Soon after, news of VITT in six U.S. patients who
took the J&J vaccine emerged as well, prompting officials to pause it to
investigate and later restrict its use. It was removed from the market entirely
two years later. AstraZeneca’s shot remained available in some parts of Europe
until May 2024, when the company requested its marketing approval be revoked due
to a decline in demand. 


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vaccine in primates

As of May 2023, the same month J&J’s vaccine was pulled, there had been 60 cases
of VITT reported in the U.S., including nine deaths. The last count for VITT
cases related to AstraZeneca’s vaccine in the U.K. before it was taken off the
market was 455, with 81 deaths, according to the U.K.'s healthcare watchdog the
Medicines and Healthcare products Regulatory Agency. 







The reactions are caused by antibodies against the protein platelet factor 4, or
PF4, a protein involved in blood clotting. In 2022, Gordon and his colleagues
used a screening method called antibody proteomics to show that antibodies
expressed by a variant of IGLV3-21*02 targeted PF4. Genetic analysis of
five patients who developed VITT after getting the AstraZeneca vaccine showed
that all of them had this gene variant. 

Then, in 2023, another research team reported that adenovirus infection led to
the same anti-PF4 antibodies and immune thrombocytopenia and thrombosis. The
pathogenesis was identical to VITT; this was the first signal of an “anti-PF4
disorder,” as the researchers called it, that might share its etiology. 

The two groups teamed up to validate their hypotheses. When they analyzed the
structure of the anti-PF4 antibodies from patients in each group and
superimposed them, they found they were “extremely similar,” as they wrote in
the NEJM letter. 

“Such an extraordinary level of autoantibody fingerprint identity between two
disorders—at the level of patient-derived antibodies—strongly indicates that
VITT and the anti-PF4 disorder that is associated with adenoviral infection are
a distinct class of adverse immune responses associated with viral (presumably,
adenoviral) structures,” the researchers wrote. 




RELATED

COVID-19 vaccine packed into skin patch shows promise in mice

With regards to the AstraZeneca and J&J vaccines, the findings concretely
implicate the adenovirus as the cause of VITT rather than other ingredients. But
while the researchers know that the immune response to the virus triggers the
creation of antibodies to PF4, they still need to identify the antigen, or the
proteins or sugars on the virus, that stimulates their creation. This would
potentially enable them to genetically engineer the adenovirus vector so it
doesn’t have the antigen and, thus, makes adenovirus-based vaccines safer. The
team behind the new NEJM paper is currently investigating the antigenic epitope,
or the part of the antigen the immune system recognizes, Gordon confirmed to
Fierce Biotech Research in an email. 

Previously, the Flinders scientists said it may be possible to create a genetic
test that can identify patients at risk of VITT as well as to come up with a
therapy that neutralizes the anti-PF4 antibodies. 

In a statement to Bloomberg earlier this week, an AstraZeneca spokesperson said
the company “welcomes any further examination of the possible underlying
mechanism of thrombosis with thrombocytopenia syndrome.” J&J told the outlet in
an email that it supports the research as well and that “more data are needed to
fully understand potential factors that may be associated with this rare
event.” 

COVID-19blood clotsvaccinesAstraZenecaJohnson & JohnsonBiotech



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