Why we might not get a coronavirus vaccine | Coronavirus outbreak | The Guardian 2020-05-25, 12:30 PM

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Why we might not get a coronavirus

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Politicians have become more cautious about immunisation
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Vaccines are simple in principle but complex in practice. Photograph: Sean Elias/PA

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Why we might not get a coronavirus vaccine | Coronavirus outbreak | The Guardian 2020-05-25, 12:30 PM

Ian Sample Science editor

@iansample
Fri 22 May 2020 11.23 BST

10,950

It would be hard to overstate the importance of developing a vaccine to Sars-

CoV-2 – it’s seen as the fast track to a return to normal life. That’s why the
health secretary, Matt Hancock, said the UK was “throwing everything at it”.

But while trials have been launched and manufacturing deals already signed
– Oxford University is now recruiting 10,000 volunteers for the next phase of
its research – ministers and their advisers have become noticeably more
cautious in recent days.

This is why.

Why might a vaccine fail?

Earlier this week, England’s deputy chief medical officer Jonathan Van-Tam
said the words nobody wanted to hear: “We can’t be sure we will get a
vaccine.”

But he was right to be circumspect.

Vaccines are simple in principle but complex in practice. The ideal vaccine
protects against infection, prevents its spread, and does so safely. But none
of this is easily achieved, as vaccine timelines show.

More than 30 years after scientists isolated HIV, the virus that causes Aids,
we have no vaccine. The dengue fever virus was identified in 1943, but the
first vaccine was approved only last year, and even then amid concerns it
made the infection worse in some people. The fastest vaccine ever
developed was for mumps. It took four years.

Scientists have worked on coronavirus vaccines

before, so are not starting from scratch. Two
coronaviruses have caused lethal outbreaks before,
namely Sars and Mers, and vaccine research went
ahead for both. But none have been licensed, partly
because Sars fizzled out and Mers is regional to the
Middle East. The lessons learned will help scientists
create a vaccine for Sars-CoV-2, but there is still an
awful lot to learn about the virus.

A chief concern is that coronaviruses do not tend to

trigger long-lasting immunity. About a quarter of
common colds are caused by human coronaviruses, but the immune
response fades so rapidly that people can become reinfected the next year.

Researchers at Oxford University recently analysed blood from recovered

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Why we might not get a coronavirus vaccine | Coronavirus outbreak | The Guardian 2020-05-25, 12:30 PM

Covid-19 patients and found that levels of IgG antibodies – those responsible
for longer-lasting immunity – rose steeply in the first month of infection but
then began to fall again.

Last week, scientists at Rockefeller University in New York found that most
people who recovered from Covid-19 without going into hospital did not
make many killer antibodies against the virus.

“That’s what is particularly challenging,” says Stanley Perlman, a veteran

coronavirus researcher at the University of Iowa. “If the natural infection
doesn’t give you that much immunity except when it’s a severe infection,
what will a vaccine do? It could be better, but we don’t know.” If a vaccine
only protects for a year, the virus will be with us for some time.

The genetic stability of the virus matters too. Some viruses, such as
influenza, mutate so rapidly that vaccine developers have to release new
formulations each year. The rapid evolution of HIV is a major reason we have
no vaccine for the disease.

So far, the Sars-CoV-2 coronavirus seems fairly stable, but it is acquiring

mutations, as all viruses do. Some genetic changes have been spotted in the
virus’s protein “spikes” which are the basis of most vaccines. If the spike
protein mutates too much, the antibodies produced by a vaccine will
effectively be out of date and might not bind the virus effectively enough to
prevent infection.

Martin Hibberd, professor of emerging infectious diseases at the London

School of Hygiene and Tropical Medicine, who helped identify some of the
virus’s mutations, called them “an early warning”.

Another challenge: making any vaccine safe

In the rush to develop a vaccine – there are now more than 100 in
development – safety must remain a priority. Unlike experimental drugs for
the severely ill, the vaccine will be given to potentially billions of generally
healthy people.

This means scientists will have to check extremely carefully for signs of
dangerous side-effects. During the search for a Sars vaccine in 2004,
scientists found that one candidate caused hepatitis in ferrets. Another
serious concern is “antibody-induced enhancement” where the antibodies
produced by a vaccine actually make future infections worse. The effect
caused serious lung damage in animals given experimental vaccines for both
Sars and Mers.

John McCauley, director of the Worldwide Influenza Centre at the Francis

Crick Institute, says it takes time to understand the particular challenges
each vaccine throws up. “You don’t know the difficulties, the specific
difficulties, that every vaccine will give you,” he says. “And we haven’t got
experience in handling this virus or the components of the virus.”

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Why we might not get a coronavirus vaccine | Coronavirus outbreak | The Guardian 2020-05-25, 12:30 PM

We should ‘end up with something’ … but what does that mean?

When the prime minister, Boris Johnson, told a No 10 press briefing that a
vaccine was “by no means guaranteed”, his chief scientific adviser, Patrick
Vallance, agreed, but added: “I’d be surprised if we didn’t end up with
something.” Many scientists share that view.

In all likelihood, a coronavirus vaccine will not be 100% effective.

Those in development draw on at least eight different approaches, from

weakened and inactivated viruses to technologies that smuggle genetic code
into the recipient’s cells, which then churn out spike proteins for the
immune system to make antibodies against.

Ideally, a vaccine will generate persistent, high levels of antibodies to wipe

out the virus and also “T” cells to destroy infected cells. But each vaccine is
different and today no one knows what kind of immune response is good
enough.

“We don’t even know if a vaccine can produce an immune response which
would protect against future infection,” says David Heymann, who led the
response of the World Health Organization (WHO) to the Sars epidemic.

Early results from two frontrunner vaccines suggest they might have some
use.

The US biotech firm Moderna reported antibody levels similar to those found
in recovered patients in 25 people who received its vaccine.

Another vaccine from Oxford University did not stop monkeys contracting
the virus, but did appear to prevent pneumonia, a major cause of death in
coronavirus patients.

If humans react the same way, vaccinated people would still spread the
virus, but be less likely to die from it.

How well a vaccine works determines how it is used. Armed with a highly
effective vaccine that protects for several years, countries could aim for herd
immunity by protecting at least two-thirds of the population.

Coronavirus patients pass the virus on to three others, on average, but if two
or more are immune, the outbreak will fizzle out. That is the best-case
scenario.

More likely is we will end up with a vaccine, or a number of vaccines, that are
only partially effective.

Vaccines that contain weakened strains of virus can be dangerous for older
people, but might be given to younger people with more robust immune
systems to reduce the spread of infection.

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Why we might not get a coronavirus vaccine | Coronavirus outbreak | The Guardian 2020-05-25, 12:30 PM

Meanwhile, older people might get vaccines that simple prevent infections
progressing to life-threatening pneumonia. “If you don’t have the ability to
induce immunity, you’ve got to develop a strategy for reducing serious
outcomes of infection,” says McCauley.

But partially effective vaccines have their own problems: a vaccine that
doesn’t stop the virus replicating can encourage resistant strains to evolve,
making the vaccine redundant.

So, is the virus here to stay?

The simple answer is: yes.

Hopes for eliminating the virus start with a vaccine but do not end there. “If
and when we have a vaccine, what you get is not rainbows and unicorns,”
says Larry Brilliant, CEO of Pandefense Advisory, who led the WHO’s
smallpox eradication programme. “If we are forced to choose a vaccine that
gives only one year of protection, then we are doomed to have Covid become
endemic, an infection that is always with us.”

The virus will still be tough to conquer with a vaccine that lasts for years.

“It will be harder to get rid of Covid than smallpox,” says Brilliant. With
smallpox it was at least clear who was infected, whereas people with
coronavirus can spread it without knowing. A thornier problem is that as
long as the infection rages in one country, all other nations are at risk.

As David Salisbury, the former director of immunisation at the Department

of Health, told a Chatham House webinar recently: “Unless we have a
vaccine available in unbelievable quantities that could be administered
extraordinarily quickly in all communities in the world we will have gaps in
our defences that the virus can continue to circulate in.”

Or as Brilliant puts it, the virus will “ping-pong back and forth in time and
geography”.

One proposal from Gavi, the vaccine alliance, is to boost the availability of
vaccines around the world through an “advance market commitment”. And
Brilliant believes some kind of global agreement must be hammered out
now. “We should be demanding, now, a global conference on what we’re
going to do when we get a vaccine, or if we don’t,” he says.

“If the process of getting a vaccine, testing it, proving it, manufacturing it,
planning for its delivery, and building a vaccine programme all over the
world, if that’s going to take as long as we think, then let’s fucking start
planning it now.”

How will we live with the virus?

People will have to adapt – and life will change. Heymann says we will have
to get used to extensive monitoring for infections backed up by swift
outbreak containment. People must play their part too, by maintaining

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Why we might not get a coronavirus vaccine | Coronavirus outbreak | The Guardian 2020-05-25, 12:30 PM

handwashing, physical distancing and avoiding gatherings, particularly in

enclosed spaces. Repurposed drugs are faster to test than vaccines, so we
may have an antiviral or an antibody treatment that works before a vaccine is
available, he adds. Immediate treatment when symptoms come on could at
least reduce the death rate.

Yuen Kwok-yung, a professor of infectious disease at the University of Hong

Kong, has advised his government that all social distancing can be relaxed –
but only if people wear masks in enclosed spaces such as on trains and at
work, and that no food or drink are consumed at concerts and cinemas.

At restaurants, tables will have to be shielded from each other and serving
staff will follow strict rules to prevent spreading the virus. “In our Hong Kong
perspective, the diligent and correct use of reusable masks is the most
important measure,” he says.

Sarita Jane Robinson, a psychologist who studies responses to threats at the

University of Central Lancashire, says people are still adapting to the “new
normal” and that without more interventions – such as fines for not wearing
face masks – “we could see people drifting back to old behaviours”.

We might become blase about Covid-19 deaths when life resumes and the
media move on, but the seriousness of the illness will make it harder to
ignore, she says.

One last possibility could save a lot of trouble. Some

scientists wonder whether the common cold
coronaviruses crossed into humans in the distant past
and caused similar illness before settling down. “If the
Has the coronavirus
pandemic made us virus doesn’t change there’s no reason to think that
all nicer? miraculously in five years’ time it won’t still cause
Read more pneumonia,” says Perlman. “But that’s the hope: that we
end up with a much more mild disease and you only get
a bad cold from it.”

Heymann says it is too soon to know how the pandemic will pan out. “We
don’t understand the destiny of this virus,” he says. “Will it continue to
circulate after its first pandemic? Or will it, like some other pandemic
viruses, disappear or become less virulent? That we do not know.”

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Why we might not get a coronavirus vaccine | Coronavirus outbreak | The Guardian 2020-05-25, 12:30 PM

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Why we might not get a coronavirus vaccine | Coronavirus outbreak | The Guardian 2020-05-25, 12:30 PM

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