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* Vaccines with viral vectors face longer-term challenge
* Immune system could turn on the vaccine
* Need for repeat shots seen likely as variants evolve
* UK government aware of vector immunity issue
By John Miller and Ludwig Burger
ZURICH, Feb 26 (Reuters) - Vaccines from AstraZeneca
, Russia's Gamaleya Institute and Johnson & Johnson
fight the coronavirus with another virus, leaving
scientists concerned the shots may lose potency if annual
inoculations become necessary to fight new variants.
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".
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)
