Studies show that coronavirus vaccines pose a risk known as vaccine exacerbation, which occurs when, instead of protecting from the disease, the vaccine makes the disease stronger in the person vaccinated with the virus. . Science does not fully understand the mechanism that unleashes that risk, one of the biggest obstacles so far to the development of a successful coronavirus vaccine.
Typically, researchers would take months to test animals for the possibility of such a flare-up from the vaccine. But due to the urgency to curb the spread of Covid-19, some labs are jumping straight into small-scale human testing, without waiting for the results of animal tests.
“I understand the importance of speeding up the timeline of vaccines in general, but as far as I know, doing it right with this vaccine is a terrible idea,” says Dr. Peter Hotez, dean of the National School of Tropical Medicine at the School. of Baylor Medicine.
Hotez worked on developing a vaccine against SARS, the coronavirus behind the huge 2003 outbreak, and found that when exposed to the virus, some vaccinated animals became much more seriously ill than the unvaccinated.
“There is a risk of immune exacerbation,” says Hotez. “And the way to rule out that risk is to make sure it doesn’t happen in laboratory animals.”
Last week, Hotez testified before the United States House of Representatives Committee on Science, Space and Technology about the need to sustainably fund vaccine research. There is no vaccine for any of the new coronaviruses that caused outbreaks in the past 20 years.
A risk worth taking
At least for now, world experts have concluded that speeding up testing is a risk worth taking.
At a meeting of the World Health Organization (WHO) in mid-February, especially convened to coordinate the global response to the new coronavirus, scientists from publicly funded research institutions and private laboratories around the world agreed that The threat was of such a magnitude that vaccine developers had to quickly move on to human testing, without waiting for the full results of the animal tests, as confirmed by four sources who attended the meeting.
“A vaccine is needed as soon as possible,” said Marie-Paule Kieny, a former WHO deputy director-general and one of the coordinators of the February meeting. “You have to weigh that against the risk that one imposes on a very small number of people, and do everything possible to mitigate that risk to the maximum.”
–
The conclusion of the meeting, which was not open to the media, has not been officially disclosed by the WHO. Nor does it reflect the official position taken by WHO, a United Nations body charged with setting health policies worldwide.
Supervision of compliance with regulations by medical laboratories and researchers is the responsibility of the control agencies of each country. In the United States, the most powerful of those agencies is the Food and Drug Administration (FDA), which has already stated that it agrees with that consensus and will not interfere with the accelerated testing schedule.
“In responding to a public health emergency, such as the emergence of a new coronavirus, we try to apply some regulatory flexibility and consider all relevant data for each vaccine platform,” the FDA said in a statement. The agency did not comment specifically on animal testing to prevent an immune exacerbation.
Developers of coronavirus vaccines continue to be required to perform animal tests to ensure that the vaccine is non-toxic and that it helps the immune system cope with the virus.
The “Seattle Risk”
There are about 20 coronavirus vaccines under development at research institutes and laboratories, including the American Johnson & Johnson and the French Sanofi SA. The US government has already allocated more than 3 billion dollars to research coronavirus treatments and vaccines.
Moderna Inc., a biotech company working with the United States National Institutes of Health (NIH), was the first to announce that it is slated to begin human testing this month, with 45 people from Seattle.
The NIH reported that animal testing to detect the specific risk of vaccine exacerbation will go ahead simultaneously, helping to establish whether it is safe to vaccinate large numbers of people.
The plan is in line with WHO consensus and FDA requirements, says Dr. Emily Erbelding, director of the Division of Microbiology and Infectious Diseases, under the auspices of the NIH. According to a spokesperson for the agency, the tests will last about 14 months.
Dr. Gregory Poland, a virologist and vaccine investigator at the Mayo Clinic in Rochester, Minnesota, has his doubts about that approach. “It is important, but it has to be done so that scientists and people in general are sure that the vaccine is not only effective, but also safe,” says Poland.
Hotez was very surprised to learn of the green light on human testing. “If immunological exacerbation occurs in laboratory animals vaccinated with the Moderna vaccine, everything must be stopped,” says Hotez.
–
The North American immunotherapy company Inovio Pharmaceutical Inc, which is developing a vaccine in collaboration with a company from China, also expects to start human tests in April, with 30 North American volunteers, without waiting for the results of vaccine exacerbation in laboratory animals.
“The community at large weighed all of that and decided they didn’t want to delay clinical trials. They encouraged us to get started earlier with Phase 1 of the studies,” says Joseph Kim, CEO of Inovio.
Next, the company plans to start human safety tests in China and South Korea, two countries badly hit by the virus. Kim says they hope to have some answers on the immune exacerbation question sometime this year.
For the Moderna / NIH tests, patients are already enrolling at the Kaiser Permanente Washington Health Research Institute in the city of Seattle. But the location of the tests, which was decided weeks ago, can be problematic.
To reduce the risk to volunteers, the scientists present at the WHO meeting recommended that laboratories restrict initial clinical trials to small groups of healthy people and carry them out in places where there is no active spread of the virus. This reduces the risk that a vaccinated volunteer will come across the virus and trigger a more severe reaction.
But ever since that location was chosen, the Seattle metropolitan area has become one of the outbreak epicenters in the United States. In Washington state, where Seattle is located, 162 cases and 22 deaths were reported, out of a total of 755 sick and 26 dead across the United States as of Tuesday, according to a count by John Hopkins University.
The Moderna and NIH plan, however, continues.
“We believe there is no reason to change locations. If we do, in the next few weeks there may be community transmission elsewhere,” says Erbelding. “The risk to volunteers is minimal and manageable as testing progresses. Participants are closely monitored at all times.”
Translation by Jaime Arrambide
—
