London/Chicago - The first wave of the
Covid-19 pandemic may be waning. For vaccine developers, that
could be a problem.
Scientists in Europe and the United States say the relative
success of draconian lockdown and social distancing policies in
some areas and countries means virus transmission rates may be
at such low levels that there is not enough disease circulating
to truly test potential vaccines.
They may need to look further afield, to pandemic hotspots
in Africa and Latin America, to get convincing results.
"Ironically, if we're really successful using public health
measures to stamp out the hot spots of viral infection, it will
be harder to test the vaccine," said Francis Collins, director
of the National Institutes of Health in the United States.
A vaccine is seen as essential to ending a pandemic that has
killed nearly 370 000 people and infected more than 6 million so
far, with world leaders looking at inoculation as the only real
way to restart their stalled economies.
But running large-scale clinical trials of potential
vaccines against a completely new disease at speed is complex,
scientists say. Showing efficacy in those trials during a
fluctuating pandemic adds extra difficulty - and doing so when
outbreaks are waning makes it harder still.
"For this to work, people need to have a risk of infection
in the community. If the virus has been temporarily cleared out,
then the exercise is futile," said Ayfer Ali, an expert in drug
repurposing at Britain's Warwick Business School.
"The solution is to move to areas where the infection is
being spread widely in the community – that would be countries
like Brazil and Mexico at the moment."
Vaccine trials work by randomly dividing people into a
treatment group and a control group, with the treatment group
getting the experimental trial vaccine and the control group
getting a placebo.
All participants go back into the community where the
disease is circulating, and subsequent rates of infection are
compared. The hope is that infections within the control group
will be higher, showing the trial vaccine is protecting the
other group.
With Covid-19 epidemics in Britain, mainland Europe and the
United States coming down from their peak and transmission rates
of the coronavirus dropping, a key task for scientists is to
chase fluctuating outbreaks and seek volunteers in sections of
populations or in countries where the disease is still rife.
A similar problem emerged when scientists were seeking to
test potential new vaccines against Ebola during the vast 2014
outbreak in West Africa. Then, drugmakers were forced to
drastically scale back plans for large trials because their
vaccines were only test-ready late in the epidemic when case
numbers were dwindling.
LOOKING ABROAD
Among the first Covid-19 vaccines to move into phase two, or
mid-stage, trials is one from the US biotech company Moderna
and another being developed by scientists at Oxford
University supported by AstraZeneca. The United States
in July is planning to launch vast efficacy trials of 20,000 to
30,000 volunteers per vaccine.
Collins said US health officials will tap government and
industry clinical trial networks in the United States first and
use mapping to detect where the virus is most active. They will
also consider looking abroad if domestic disease rates fall too
far, he said.
The US government has experience in Africa of testing
vaccines against HIV, malaria and tuberculosis.
"Africa is now beginning to experience lots of cases of
Covid-19. We might very well want to run part of the trial
there, where we know we can collect the data effectively," said
Collins.
Adrian Hill, director of the Jenner Institute at Britain's
Oxford University which has teamed up with AstraZeneca, started
mid-stage trials last month which he said would aim to recruit
around 10,000 people in Britain.
He told Reuters that with Covid-19 disease transmission
rates dropping in the UK there is a possibility that the trial
would have to be halted if they didn't have enough infections to
yield a result.
"That would be disappointing, and at the moment it's
unlikely, but it's certainly a possibility," Hill said.
CHALLENGE TRIALS
Underscoring the level of concern in the industry,
AstraZeneca's chief executive Pascal Soriot said his researchers
were even contemplating running so-called "challenge" trials -
where participants would be given the experimental vaccine and
then deliberately infected with Covid-19 to see if it worked.
Such trials are rare, high risk and hard to get ethical approval
for.
As a more practical and swifter option, Soriot and others
are looking to Brazil and other countries in South America, as
well as parts of Africa where Covid-19 outbreaks are still
growing and peaking, as ripe drug and vaccine testing grounds.
Difficulty recruiting candidates for mid-stage vaccine
trials in countries where the Covid-19 pandemic is on the wane
may be foreshadowed by the experience of doctors seeking
infected cases for the World Health Organization's multi-country
Solidarity trial of potential treatments for the disease -
including the generic drug hydroxychloroquine and Gilead's
remdesivir.
In the Swiss portion of that trial, for instance, it took
three weeks to get all of the ethical and regulatory approvals
from authorities, and another week to get all the drugs, said
Oriol Manuel, an infectious disease expert and national
coordinator of the Solidarity study in Switzerland.
"We were able to enroll some patients in (one trial centre
in) Lausanne," Manuel said. "But when all centres were ready,
the cases were fortunately disappearing."