On March 16, local time, the first of dozens of healthy volunteers in Seattle, Washington, were vaccinated in a U.S. government-sponsored safety trial. This is an mRNA vaccine developed by the National Institute of Allergy and Infectious Diseases (NIAID) and biopharmaceutical company Moderna. The vaccine was prepared about 6 weeks after the release of the new coronavirus gene sequence (February 24) and entered phase one clinical trial less than 10 weeks, although it has yet to complete animal trials.
The vaccine, known as the world’s first clinical trial, could set two records if approved: the fastest vaccine in history and the first mRNA vaccine to be used for vaccination.
As more and more vaccine trials begin, still remains unanswered about how people’s immune systems fight the virus and how to safely use vaccines to trigger similar immune responses.
Some researchers say the lack of information should not prevent experts from starting human safety trials.
Others worry that if the candidate vaccine for accelerated testing turns out to be ineffective or unsafe, it could lead researchers to start over and eventually delay the development and rollout of effective vaccines.
In response, an article published online in the journal Nature interviewed relevant American scientists. Here are some of the key questions scientists hope to answer when developing a coronavirus vaccine.
Will people be immune?
Vaccines help people to respond to infections without first exposure to pathogens. Studies of other coronaviruses, such as the four coronaviruses that cause certain common colds, have led most researchers to believe that people recovering from neo-coronavirus infection will not be infected again for some time.
But Michael Diamond, a virologist at the University of Washington, says this hypothesis needs to be supported by evidence. “We know very little about the virus’s immunity. “
On March 14th China published a preprinted article examining two rhesus monkeys recovering from a new coronavirus infection. New coronavirus infection only causes mild illness.
When the researchers exposed the monkeys again four weeks after their first exposure to the virus, they did not appear to be infected again. Diamond said researchers will look for evidence that people respond in the same way.
If immunity is generated, how long will it last?
This is another huge unknown. Immunity is short-lived for coronaviruses that cause the common cold; even people with high levels of antibodies to these viruses can be infected, said Stanley Perlman, a coronavirusologist at the University of Iowa.
The evidence is more vague about the two other coronaviruses that cause the epidemic, the coronavirus that causes severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS).
Perlman said his team found that when MERS patients recover, the antibodies in the body drop sharply. He added that his team had collected data ( not yet published ) to show that SARS antibodies still exist in the body 15 years after the infection.
But it is unclear whether this immune response is sufficient to prevent reinfection. “We don’t have good evidence of long-term immunity, but we don’t have really good data from SARS and MERS. Perlman added.
What kind of immune response should vaccine developers look for?
The first phase of the trial focused on the safety of vaccines developed by Moderna in Cambridge, Massachusetts. But researchers will also be keeping a close eye on the nature of the immune response triggered by the vaccine.
The Moderna vaccine consists of an RNA molecule. Like many other new coronavirus vaccines being developed, it is designed to train the immune system to produce antibodies that identify and block protoproteins used by viruses to enter human cells.
“I think this is the first reasonable approach, but maybe we’ll find that the antibody’s response to the protoprotein may not be all. Diamond said.
A successful new coronavirus vaccine may require stimulating the body to produce antibodies to block other viral proteins, for example, by making T-cells to identify and kill infected cells.
How do I know if a vaccine is likely to work?
Typically, the vaccine is tested in animals for safety and efficacy and enters human trials.
But another vaccine being developed by Moderna And Inovio Pharmaceuticals in Plymouth, Pennsylvania, is being tested in animals, while a phase-first clinical trial is under way. Inovio plans to begin its first human trials in April.
“In non-emergency situations, (trials) may be carried out in a more continuous manner. But in the present situation, a lot of things are done in parallel. Barney Graham, deputy director of the National Institutes of Health’s (NIH) Vaccine Research Center, said. NIH is sponsoring a clinical trial in Moderna.
In a preprinted article on March 2, the researchers reported that they injected mice and guinea pigs with Inovio’ vaccine, a DNA molecule that carries instructions to make protrusion proteins. They found that the animals produced antibodies and T-cells that fight the virus.
Kate Broderick, the study’s leader and inn’s senior vice president of preclinical research and development, said her team had injected monkeys with the vaccine and would soon begin studying whether vaccinated animals were infected with the new coronavirus to see if they were protected. Graham said the Moderna vaccine is also conducting similar “challenge” studies.
Without such data from animals, he added, large-scale, expensive trials of a vaccine to prevent human infection scanted would not be possible. Diamond predicts that as researchers learn more about infections from human and animal studies, they will be able to better understand which vaccine might be most effective. “This may not be the most effective way. But this may be the easiest way to make a vaccine. Diamond said.
Is it safe?
Because vaccines are used in large numbers of healthy people, vaccines often have higher safety standards than drugs used for people who are already sick. For the new coronavirus vaccine, the researchers’ main safety concern is to avoid a phenomenon called disease enhancement.
In this case, people who have been vaccinated do have the disease, but they suffer from a more serious disease than those who have never been vaccinated.
In a 2004 study of an experimental SARS vaccine, the vaccinated ferret developed devastating inflammation in the liver after contracting the virus.
Peter Hotez, a vaccine scientist at Baylor College of Medicine in Houston, Texas, says potential vaccines should be tested in animals first to rule out increased disease before being tested in humans.
He said he understood the reasons for quickly pushing the new crown vaccine to human trials, but added that because the vaccine could exacerbate the disease, “I’m not sure if this is the vaccine you want.”