'They've jumped the gun': scientists worry about
Russia's Covid-19 vaccine
Rising chorus of concern over Sputnik V vaccine stems
from opaque development and lack of mass testing
Peter
Beaumont
Wed 12 Aug
2020 17.17 BSTFirst published on Wed 12 Aug 2020 13.04 BST
In 1977,
Scott Halstead, a virologist at the University of Hawaii, was studying dengue
fever when he noticed a now well-known but then unexpected feature of the
disease.
Animals
that had already been exposed to one of the four closely related viruses that
cause dengue and produced antibodies to it, far from being protected against
other versions, became sicker when infected a second time, and it was the
antibodies produced by the first infection that were responsible, allowing the
second infection to hitchhike into the body.
The effect
was called antibody-dependent enhancement (ADE). The reason it matters today,
in the midst of the coronavirus pandemic, is that unexpected glitches such as
ADE are the kind of problems vaccine developers look for in phase-3 testing of
vaccines – testing that has yet to be carried out on Russia’s newly approved
Sputnik V vaccine.
In recent
weeks, as announcements on the development of scores of vaccines around the
world have come in rapid succession, the still poorly understood mechanisms of
ADE have been thrust into the spotlight as scientists speculate on whether
vaccine-produced antibodies could trigger this effect.
ADE “is a
genuine concern”, Kevin Gilligan, a virologist and senior consultant with
Biologics Consulting, told Nature Biotechnology in June. “Because if the gun is
jumped and a vaccine is widely distributed that is disease-enhancing, that
would be worse than actually not doing any vaccination at all.”
This week,
following Russia’s announcement that it is pushing ahead with mass production
of Sputnik V and mass inoculation , the fears expressed by the likes of
Gilligan became a chorus, underlining the concerns among scientists that
Russian researchers have jumped the gun.
Russia has
described claims that the vaccine is unsafe as groundless, and on Wednesday
vowed to roll it out in two weeks. But criticism has continued to build.
Among those
mentioning ADE as a concern was Danny Altmann, a professor of immunology at
Imperial College. He said part of the problem was that the work behind Russia’s
vaccine development had been so opaque that no one really knows how safe or
even how effective it will be.
“I don’t
think the Russian researchers have done anything wrong, but I think they’ve
jumped the gun,” he told the Guardian. “If we are talking about safety then you
have to be looking at issues like ADE, which was a concern that scuppered some
efforts to develop a Sars vaccine, where it exacerbated an asthma-like response
in lungs.”
It is not
just the potential for issues such as ADE that concerns people like Altmann,
who is optimistic that the hunt for a vaccine for Covid-19 is not “intractable”.
He said the ideal approach would have been to compare 150 or so different
vaccine candidates transparently, using the same testing criteria, to ensure
the world gets the best vaccine, not simply the first.
“No two of
these candidates is going be alike in terms of safety, how effective they are
or how cheap they are to produce,” he said. “The reason we’re crying out for
transparency and peer review is because those factors are very serious. There
have been too many debacles in this pandemic. This is not another occasion to
blunder in. You want to line up the candidates side by side.”
The lack of
effective testing throws up other issues. “I think there is enough general
background data … to assume the [Russian] vaccine itself will be safe at the usual
doses,” Ian Jones, a professor of virology at the University of Reading, said
in a statement posted on the Science Media Centre website. “The bigger risk,
however, is that the immunity generated is not sufficient to give protection,
leading to continued virus spread even among immunised individuals.
“And
although only a possibility, less than complete protection could provide a
selection pressure that drives the virus to evade what antibody there is,
creating strains that then evade all vaccine responses. In that sense, a poor
vaccine is worse than no vaccine. Careful virus tracking will therefore need to
accompany any early release.”
Even before
Russia’s announcement, some were warning about accelerated vaccine development
programmes in Russia and in the US. In an opinion piece for the New York Times,
Natalie Dean, an assistant professor of biostatistics at the University of
Florida, flagged up many of the same issues, adding that she would hesitate to
take a vaccine that appeared to have been rushed through without proper
testing.
“[The]
benchmark [of phase-3 testing] is crucial because a weak vaccine might be worse
than no vaccine at all,” she said. “We do not want people who are only slightly
protected to behave as if they are invulnerable, which could exacerbate
transmission. It is also costly to roll out a vaccine, diverting attention away
from other efforts that we know work, like mask-wearing, and from testing
better vaccines.”
The last
thing phase-3 trials do is examine safety. Earlier trials do this too, but
larger trials allow for rarer side effects to be detected. One such effect is a
paradoxical phenomenon known as immune enhancement, in which a vaccinated
person’s immune system overreacts to infection. Researchers can test for this
by comparing the rates of disease severe enough to require hospitalisation
across two groups.
“A clear
signal that hospitalisation is higher among vaccinated participants would mark
the end of a vaccine,” Dean said.
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