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 So-called viral vector shots - also used by several Chinese COVID-19
vaccine developers - use harmless modified viruses as vehicles, or
vectors, to carry genetic information that helps the body build
immunity against future infections.
However, there is a risk that the body also develops immunity to the
vector itself, recognising it as an intruder and trying to destroy
it.
Most vector-vaccine developers have opted to use an adenovirus, a
harmless class of common-cold viruses."The experience with
adenoviruses has been for many years that vectors can be intercepted
by the immune system after repeat injections," said Bodo Plachter,
deputy director of the Institute of Virology at Mainz University's
teaching hospital.
"There may be the same problem with other types of vectors. Only
'trial and error' will tell," he added.
That potentially puts vector vaccines at a disadvantage to mRNA
shots from Pfizer and Moderna, or vaccines using deactivated
coronaviruses, like Sinovac's, or the coronavirus' surface spike
proteins, an approach pursued by Novavax.
Vector immunity is not a new issue but has come under renewed
scrutiny as companies including J&J anticipate regular COVID-19
vaccinations, like annual influenza shots, may be needed to combat
new variants of the coronavirus.
Moderna as well as Pfizer and partner BioNTech said in separate
statements this week they are studying additional booster shots that
target new variants over time.
Even without any evolution in the virus, it is not yet clear whether
vaccine-induced immune memory will eventually wane, which would also
require booster shots.
Scientists who spoke with Reuters acknowledged no definitive
conclusions can be drawn about vector immunity's ultimate impact.
While it may prove surmountable in the end, health policymakers will
still have to grapple with the question of which vaccines to deploy,
and in what order, ahead of potential repeat inoculations.
A major validation of vector technology was the approval of Merck &
Co's Ervebo inoculation against Ebola in 2019 and its use - and that
of similar experimental vaccines - during outbreaks in Africa in
prior years.
But vector immunity has been implicated in past failures, including
when a 2004 Merck AIDS vaccine trial flopped in men previously
exposed to the adenovirus used for the vaccine.
AstraZeneca declined to comment. J&J and the Russian Direct
Investment Fund (RDIF), which is responsible for marketing the
Sputnik vaccine made by the Gamaleya Institute abroad, did not
respond to a request for comment.
MIX AND MATCH
One approach could be to combine different shots, known as "mixing
and matching".
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 AstraZeneca and partner Oxford
University's shot is being trialled with
Russia's Sputnik V, and British scientists are
testing Pfizer's mRNA shot with AstraZeneca's
vaccine in a study funded by the British
government, which says it is aware of the vector
immunity issue.
The main motive for the British combination
trial was to give healthcare providers
flexibility in case of limited supplies, but
Matthew Snape, the Oxford vaccinologist leading
the project, said the question of vector
immunity "is one of the reasons this study is
interesting".
He added there were plans to test for any
anti-vector reaction by seeing how well a viral
vector performs versus an alternative vaccine
when given as a third dose.
Mainz University's Plachter is among those suggesting it may be more
practical over the longer term to pivot to a class of vaccine that
does not rely on vectors.
"If after a while, you get to a standard immunization protocol, as
with influenza, I would assume you would use other carriers," he
said. AstraZeneca and the Gamaleya Institute have already sought to
overcome vector immunity challenges under the standard COVID-19
two-shot regimen. The Russian lab employed two different viral
vectors, seeking to prevent efficacy dropping from the primary dose
to the booster shot, while AstraZeneca and Oxford use a chimpanzee
virus vector to which humans would not previously have been exposed.
But questions over a third or subsequent shot have yet to be
addressed.
"One of the big sells for (AstraZeneca) was that there can be no
existing immunity," Ian Jones, a professor of virology at Reading
University, said. "This will not be the case once the world has had
the COVID vaccines."
Since the vectors in the leading vaccines have been stripped of
their ability to replicate, the antibody and T-cell responses they
generate may, however, not be that strong.
Moreover, only tiny vector volumes are needed for COVID-19 vaccines,
in contrast with gene therapies where viral vectors serve as gene
repair kits for diseased cells and vector immunity needs to be
monitored closely because much larger quantities are injected.
"The injected dose is so low that the induction of immunity to the
capsid, or virus shell, remains low," said Luk Vandenberghe, a
Harvard Medical School gene therapy expert working on a viral-vector
COVID-19 vaccine.
(Reporting by Ludwig Burger in Frankfurt, John Miller in Zurich,
Kate Kelland and Alistair Smout in London and Michael Erman in New
York; Editing by Josephine Mason and Kirsten Donovan)
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