As pressure for coronavirus vaccine mounts, scientists debate risks of accelerated testing/ Reuters
Normally, researchers would take months to test for the
possibility of vaccine enhancement in animals. Given the urgency to stem the
spread of the new coronavirus, some drugmakers are moving straight into
small-scale human tests, without waiting for the completion of such animal
tests.
possibility of vaccine enhancement in animals. Given the urgency to stem the
spread of the new coronavirus, some drugmakers are moving straight into
small-scale human tests, without waiting for the completion of such animal
tests.
“I understand the importance of accelerating timelines for
vaccines in general, but from everything I know, this is not the vaccine to be
doing it with,” Dr Peter Hotez, dean of the National School of Tropical
Medicine at Baylor College of Medicine, told Reuters.
vaccines in general, but from everything I know, this is not the vaccine to be
doing it with,” Dr Peter Hotez, dean of the National School of Tropical
Medicine at Baylor College of Medicine, told Reuters.
Hotez worked on development of a vaccine for SARS (Severe Acute
Respiratory Syndrome), the coronavirus behind a major 2003 outbreak, and found
that some vaccinated animals developed more severe disease compared with
unvaccinated animals when they were exposed to the virus.
Respiratory Syndrome), the coronavirus behind a major 2003 outbreak, and found
that some vaccinated animals developed more severe disease compared with
unvaccinated animals when they were exposed to the virus.
“There is a risk of immune enhancement,” said Hotez. “The way
you reduce that risk is first you show it does not occur in laboratory
animals.”
you reduce that risk is first you show it does not occur in laboratory
animals.”
Hotez testified last week before the U.S. House Committee on
Science, Space and Technology about the need for sustained funding for vaccine
research. There remains no vaccine for any of the new coronaviruses that have
caused outbreaks in the past 20 years.
Science, Space and Technology about the need for sustained funding for vaccine
research. There remains no vaccine for any of the new coronaviruses that have
caused outbreaks in the past 20 years.
At least for now, the world’s experts have concluded that
accelerated testing is a risk worth taking.
accelerated testing is a risk worth taking.
At a specially convened World Health Organization (WHO) meeting
in mid-February, designed to co-ordinate a global response to the new
coronavirus, scientists representing government-funded research organizations
and drugmakers around the world agreed that the threat was so great that
vaccine developers should move quickly into human trials, before animal testing
is completed, four people who attended the meeting told Reuters.
in mid-February, designed to co-ordinate a global response to the new
coronavirus, scientists representing government-funded research organizations
and drugmakers around the world agreed that the threat was so great that
vaccine developers should move quickly into human trials, before animal testing
is completed, four people who attended the meeting told Reuters.
“You want to have a vaccine as quickly as possible,” Dr
Marie-Paule Kieny, former assistant director-general at the WHO, who co-chaired
the meeting, told Reuters. “You have to balance this with the risk that you impose
on a very small number of people, and do all you can do to mitigate this risk
as much as possible.”
Marie-Paule Kieny, former assistant director-general at the WHO, who co-chaired
the meeting, told Reuters. “You have to balance this with the risk that you impose
on a very small number of people, and do all you can do to mitigate this risk
as much as possible.”
The conclusion of that meeting, which was not open to media, has
not been officially publicized by the WHO. It does not reflect any official
position adopted by the WHO, a United Nations body whose job it is to help
shape global health policy.
not been officially publicized by the WHO. It does not reflect any official
position adopted by the WHO, a United Nations body whose job it is to help
shape global health policy.
Regulatory oversight of drugmakers and medical research is in
the hands of national regulators. The most powerful of those, the U.S. Food and
Drug Administration (FDA), has signaled that it is in agreement with the
consensus and will not stand in the way of accelerated testing schedules.
the hands of national regulators. The most powerful of those, the U.S. Food and
Drug Administration (FDA), has signaled that it is in agreement with the
consensus and will not stand in the way of accelerated testing schedules.
“When responding to an urgent public health situation such as
novel coronavirus, we intend to exercise regulatory flexibility and consider
all data relevant to a certain vaccine platform,” FDA spokeswoman Stephanie
Caccomo said in a statement. The agency had no comment specifically on animal
testing for vaccine enhancement.
novel coronavirus, we intend to exercise regulatory flexibility and consider
all data relevant to a certain vaccine platform,” FDA spokeswoman Stephanie
Caccomo said in a statement. The agency had no comment specifically on animal
testing for vaccine enhancement.
Coronavirus vaccine developers are still required to conduct
routine animal testing to make sure the vaccine itself is not toxic and is
likely to help the immune system respond to the virus.
routine animal testing to make sure the vaccine itself is not toxic and is
likely to help the immune system respond to the virus.
SEATTLE
RISK
RISK
Some 20 coronavirus vaccine candidates are being developed by
research institutes and drugmakers including America’s Johnson & Johnson
and France’s Sanofi SA. The U.S. government has earmarked more than $3 billion
for coronavirus treatments and vaccines.
research institutes and drugmakers including America’s Johnson & Johnson
and France’s Sanofi SA. The U.S. government has earmarked more than $3 billion
for coronavirus treatments and vaccines.
Biotechnology company Moderna Inc, which is working with the
U.S.-funded National Institutes of Health (NIH), is the closest to human
testing, announcing plans to start a trial with 45 people in Seattle this
month.
U.S.-funded National Institutes of Health (NIH), is the closest to human
testing, announcing plans to start a trial with 45 people in Seattle this
month.
Testing for the specific risk of vaccine enhancement in animals
will proceed simultaneously with human trials, the NIH told Reuters, which it
said should establish whether it is safe to expose larger numbers of people to
the vaccine. Moderna did not respond to requests for comment.
will proceed simultaneously with human trials, the NIH told Reuters, which it
said should establish whether it is safe to expose larger numbers of people to
the vaccine. Moderna did not respond to requests for comment.
The plan is consistent with the WHO consensus and FDA
requirements, said Dr Emily Erbelding, director of the Division of Microbiology
and Infectious Diseases of the National Institute of Allergy and Infectious
Diseases (NIAID), part of the NIH. The trial is expected to take 14 months, a
spokeswoman for the NIH said.
requirements, said Dr Emily Erbelding, director of the Division of Microbiology
and Infectious Diseases of the National Institute of Allergy and Infectious
Diseases (NIAID), part of the NIH. The trial is expected to take 14 months, a
spokeswoman for the NIH said.
Dr Gregory Poland, a virologist and vaccine researcher with the
Mayo Clinic in Rochester, Minnesota, expressed doubts about that approach.
“This is important, but it has to be done in a way that reassures scientists
and the public that these (vaccines) are not only efficacious, but safe,” he
told Reuters.
Mayo Clinic in Rochester, Minnesota, expressed doubts about that approach.
“This is important, but it has to be done in a way that reassures scientists
and the public that these (vaccines) are not only efficacious, but safe,” he
told Reuters.
Hotez said he was surprised human trials were going ahead. “If
there is immune enhancement in laboratory animals vaccinated with the Moderna
vaccine, that’s a showstopper,” he said.
there is immune enhancement in laboratory animals vaccinated with the Moderna
vaccine, that’s a showstopper,” he said.
U.S. immunotherapy company Inovio Pharmaceuticals Inc, which is
developing a coronavirus vaccine in collaboration with a Chinese company, also
expects to start human clinical trials in 30 U.S. volunteers in April rather
than wait for animal studies on vaccine enhancement.
developing a coronavirus vaccine in collaboration with a Chinese company, also
expects to start human clinical trials in 30 U.S. volunteers in April rather
than wait for animal studies on vaccine enhancement.
“The community as a whole weighed that and said we don’t want to
delay the clinical process. We’ve been encouraged to go as rapidly as possible
into Phase 1 studies,” Inovio Chief Executive Joseph Kim told Reuters.
delay the clinical process. We’ve been encouraged to go as rapidly as possible
into Phase 1 studies,” Inovio Chief Executive Joseph Kim told Reuters.
The company plans to start human safety trials shortly
thereafter in China and South Korea – two countries that have been hit hard by
the virus. Kim said he expects to have an answer to the question of vaccine
enhancement at some point this year.
thereafter in China and South Korea – two countries that have been hit hard by
the virus. Kim said he expects to have an answer to the question of vaccine
enhancement at some point this year.
The Moderna/NIH trial is enrolling patients at the Kaiser
Permanente Washington Health Research Institute in Seattle. The choice of
location, made several weeks ago, could prove to be problematic.
Permanente Washington Health Research Institute in Seattle. The choice of
location, made several weeks ago, could prove to be problematic.
To reduce the risk to volunteers, scientists at the WHO meeting
recommended that drugmakers restrict early clinical trials to small groups of
healthy people and conduct them in places where the virus is not spreading,
according to Kieny, who now works at French research institute Inserm. That
lowers the chances that people who get the vaccine could encounter the virus
and trigger a more severe reaction.
recommended that drugmakers restrict early clinical trials to small groups of
healthy people and conduct them in places where the virus is not spreading,
according to Kieny, who now works at French research institute Inserm. That
lowers the chances that people who get the vaccine could encounter the virus
and trigger a more severe reaction.
Since the location was chosen, the Seattle metro area has
emerged as the epicenter of infections in the United States. Washington state
has reported 162 coronavirus infections and 22 deaths, out of a total of 755
infections and 26 deaths in the country as of Tuesday, according to a tally by
Johns Hopkins University.
emerged as the epicenter of infections in the United States. Washington state
has reported 162 coronavirus infections and 22 deaths, out of a total of 755
infections and 26 deaths in the country as of Tuesday, according to a tally by
Johns Hopkins University.
Nevertheless, Moderna and the NIH plan to go ahead.
“We think there is no reason to have to change the site. If you
change it, there might be community transmission in another site over the next
couple of weeks,” Erbelding said. “Any risk of that to participants is very
small. It would be manageable as the trial progresses. People are being observed
very, very carefully.”
change it, there might be community transmission in another site over the next
couple of weeks,” Erbelding said. “Any risk of that to participants is very
small. It would be manageable as the trial progresses. People are being observed
very, very carefully.”
EARLY
WARNING SIGNS
WARNING SIGNS
Tragic lessons from other vaccines and prior work on
coronaviruses have raised some warning flags for developers.
coronaviruses have raised some warning flags for developers.
The best-known example occurred in a U.S. trial in the 1960s of
a vaccine created by the NIH and licensed to Pfizer Inc to fight respiratory
syncytial virus (RSV), which causes pneumonia in infants. The vast majority of
babies who received the vaccine developed more severe disease, and two toddlers
died. A more recent example occurred in the Philippines, where some 800,000
children were vaccinated with Sanofi’s dengue vaccine, Dengvaxia. Only
afterward did the company learn that it could increase the risk of more severe
disease in a small percentage of individuals.
a vaccine created by the NIH and licensed to Pfizer Inc to fight respiratory
syncytial virus (RSV), which causes pneumonia in infants. The vast majority of
babies who received the vaccine developed more severe disease, and two toddlers
died. A more recent example occurred in the Philippines, where some 800,000
children were vaccinated with Sanofi’s dengue vaccine, Dengvaxia. Only
afterward did the company learn that it could increase the risk of more severe
disease in a small percentage of individuals.
Research, including that conducted by Hotez, has shown that
coronaviruses in particular have the potential to produce this kind of
response. But testing for the risk of vaccine enhancement is time-consuming
because it requires scientists to breed mice that are genetically altered to
respond to the virus like humans. Work on these and other animal models is just
getting under way in several laboratories around the world.
coronaviruses in particular have the potential to produce this kind of
response. But testing for the risk of vaccine enhancement is time-consuming
because it requires scientists to breed mice that are genetically altered to
respond to the virus like humans. Work on these and other animal models is just
getting under way in several laboratories around the world.
Moderna, Inovio and several other vaccine developers are not
waiting for that process to be completed and are planning to launch human
trials in record time for a virus that was only discovered in December.
waiting for that process to be completed and are planning to launch human
trials in record time for a virus that was only discovered in December.
Both Moderna and Inovio say their vaccines are likely to have a
lower risk of vaccine enhancement because they are made using newer technology
that focuses on specific genes on the outer ‘spike’ portion of the virus.
Coronavirus vaccines that caused vaccine enhancement were typically made using
an inactivated version of the entire virus. Neither company has produced a
licensed vaccine to date.
lower risk of vaccine enhancement because they are made using newer technology
that focuses on specific genes on the outer ‘spike’ portion of the virus.
Coronavirus vaccines that caused vaccine enhancement were typically made using
an inactivated version of the entire virus. Neither company has produced a
licensed vaccine to date.
J&J said it is developing animal models to test for vaccine
enhancement and hopes to have a vaccine candidate ready for human trials in
October. A Sanofi spokeswoman said the company will examine this risk before
testing the vaccine in clinical trials.
enhancement and hopes to have a vaccine candidate ready for human trials in
October. A Sanofi spokeswoman said the company will examine this risk before
testing the vaccine in clinical trials.
“People know how traumatic the RSV experience was,” said Dr
Johan Van Hoof, global head of Janssen Vaccines, J&J’s vaccine unit. “When
you see signals in animals like this, we should not ignore them.”
Johan Van Hoof, global head of Janssen Vaccines, J&J’s vaccine unit. “When
you see signals in animals like this, we should not ignore them.”
By the Way. Just a heads up!
Anyone who has gotten the flu shot is at a 36% higher risk of catching Covid-19.
See: Wolff, Greg G., Vaccine Volume 38, Issue 2, 10 January 2020, Pages 350-354
https://www.sciencedirect.com/science/article/pii/S0264410X19313647?via%3Dihub
Possibly true