BackAs Covid-19 vaccine development pushes ahead, researchers probe safety
Among potential concerns is rare complication that could worsen coronavirus’s severity
PremiumIn 2017, researchers found that some children who got a new vaccine against the tropical disease dengue later came down with a severe case of the illness, forcing production to temporarily stop. Now, researchers developing coronavirus vaccines aim to avoid a similar fate that could set back fast-moving efforts to curb the pandemic.
The researchers say they have designed Covid-19 vaccines in ways that aim to make sure they fight off infections, rather than worsen them.
The large, final-stage trials starting to get under way will look for signs of rare side effects like the ones that arose for vaccines for dengue and other respiratory conditions, including other coronaviruses. The rare complication, known as disease enhancement because it worsens the disease the vaccine is supposed to protect against, is a concern for vaccine research generally.
“I think it’s important that we do rapid vaccine development, but I also think it’s important we do it safely," said Dr Barney Graham, deputy director of the vaccine research center at the National Institute of Allergy and Infectious Disease.
He said he hasn’t seen any areas of concern in testing to date for the coronavirus vaccines.
Moderna Inc, Pfizer Inc and other companies say their coronavirus vaccines have shown to be generally safe and well-tolerated in early-stage testing in small numbers of people.
Vaccines are designed to produce immune-system agents, including antibodies, that lock onto a virus and thereby neutralize it. In cases of disease enhancement, however, immune agents act in ways that facilitate replication of the virus.
The complication can dangerously increase the severity of the disease in people exposed to the pathogen after they get the shots.
Aside from affecting Sanofi SA’s dengue vaccine Dengvaxia, signs of disease enhancement stymied development of an experimental vaccine against respiratory syncytial virus, or RSV, after studies in children in the mid-1960s detected the side effect.
The safety issue has hovered over efforts to bring to market a vaccine for the new coronavirus because signs of disease enhancement arose in research into vaccines for other coronaviruses.
Researchers studying experimental vaccines against the coronavirus that caused an outbreak of severe acute respiratory syndrome, or SARS, in 2002 found that vaccinated mice developed enhanced disease when exposed to the virus. No SARS vaccines have been approved for humans.
To avoid the complication, coronavirus vaccine researchers have taken steps such as making available high-quality antigens, something the vaccine either delivers to or produces in the body to trigger a desired immune response.
Some researchers have designed antigens based on the “spike" protein found on the surface of the coronavirus, Dr Graham said. The virus uses the spike protein to latch onto human cells and gain entry.
Some vaccines under development contain something resembling the spike protein itself while others carry genetic code instructing the body’s own cells to make that protein.
By focusing on the spike protein, a vaccine could primarily generate enough “neutralizing" antibodies to block the virus, Dr Graham said, and potentially avoid spawning too many other immune-system agents that may attach to other parts of the virus and are suspected in disease enhancement. He said this will have to be proven in studies.
While researchers have targeted the spike protein in experimental vaccines for Middle East Respiratory Syndrome and SARS, none have advanced to be approved for broad use.
Johnson & Johnson, which is developing a vaccine targeting the spike protein and expected to start human testing this month, says its technology is designed to elicit high levels of neutralizing antibodies and a type of response from other immune-system agents known as T-cells.
The design could reduce the risk of vaccine-associated disease enhancement, said Hanneke Schuitemaker, head of viral vaccine discovery at J&J.
Because vaccines are given to healthy people to prevent disease—rather than a treatment given to a sick person—the threshold for safety is typically higher than for drugs.
About 20 coronavirus vaccines are in human testing, and 140 more are in development, according to the World Health Organization.
The final stage, or phase 3, trials starting this month will prove crucial to establishing that coronavirus vaccines don’t raise the risk of disease enhancement, researchers say, because the studies will test in tens of thousands of subjects the same doses the public is expected to receive if the shots are authorized for use.
“You won’t know that is happening until you have somebody who got vaccinated and then was exposed," National Institutes of Health Director Francis Collins said in an interview, referring to the risk for disease enhancement.
In small, early-stage studies, some coronavirus vaccine subjects experienced transient fevers or sore arms after vaccinations, companies said. The side effects, unrelated to disease enhancement, appeared more pronounced in people who received the highest doses tested, the companies said.
Similar side effects have been seen in older vaccines commonly used for other diseases.
Carol Kelly received the second of two doses of Moderna’s experimental vaccine in May, in a clinical trial at Emory University in Atlanta. The next morning, the 61-year-old dietitian said, she woke up with a feeling of vertigo “and about a half a thimble full of energy."
The rest of the day, she said, she felt fatigued and had a headache. She took pain relievers, and the symptoms were gone by the next day and she has felt fine ever since, she said.
Moderna Chief Medical Officer Tal Zaks said the company expected some people to have adverse reactions, and one of the main purposes of early testing is to find which dose levels are safest.
Certain reactions, such as fatigue, can be a signal that the vaccine has set in motion the desired immune response, he said. “You’re paying a price in some symptoms to educate the immune system" to prepare a defense against the coronavirus, Dr Zaks said in an interview.
Jared Hopkins contributed to this article
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