The candidate vaccine will likely be based on a new technology that has been tested in animals and gone through early-stage trials in people, but has yet to receive regulatory approval against any disease.
A so-called mRNA vaccine can be made quickly -- without needing to be grown in chicken eggs, as is the flu vaccine, for instance. A company in the Boston area is already working to design an mRNA vaccine based on the genetic sequence of the new coronavirus released by the Chinese government this month.
“It’s not the only candidate we’re involved with, but we’re moving quickly on that,” says Anthony Fauci, MD, the longtime head of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
Early trials in people suggest that such a vaccine can stimulate an immune response very well. But it has never been tried during an outbreak.
How mRNA Vaccines Work
Scientists design an mRNA vaccine to carry instructions for making the same proteins found on the outside of a particular type of virus -- in this case, the new coronavirus. These proteins prime the body’s immune system to make antibodies against that virus, and therefore to be ready to fight off any actual infection from that virus, says Tal Zaks, MD, PhD, chief medical officer of Moderna Inc., the Cambridge, MA-based biotechnology company that is rushing to develop an mRNA vaccine against the new coronavirus.
“All we are doing is piggybacking,” Zaks says, “so to the immune system, it looks like there’s an infection.”
With SARS, or severe acute respiratory syndrome, a lethal coronavirus that caused outbreaks in Hong Kong, Canada, and elsewhere in 2002-2003, the virus was controlled with public health measures and contained before a vaccine could be developed. The new virus, which seems to have started in a wild animal market in Wuhan, China, in mid-December, is already raging across China and may have spread too far to control with public health measures.
Zaks says all early indications about the mRNA approach are positive. Roughly 1,000 people have received different versions of mRNA vaccines so far in seven clinical trials designed to prevent other respiratory viruses, including a strain of the flu, respiratory syncytial virus (RSV), and human metapneumovirus (HMPV).
Many had typical vaccine side effects, including sore arms and low-grade, flu-like symptoms for a day or more, but nothing more serious, he says. “We’ve dosed over 1,000 subjects and not seen anything surprising or untoward,” Zaks says.
The vaccine appeared to generate a robust immune response comparable to one in people who had recovered from the virus, he says.
Older people, who normally have weaker immune responses, benefited as much as younger ones, Zaks says. “Based on the fundamental immunology and the initial data we have, my expectation is that it will work in older adults as well as it does in younger adults,” he says.
But that remains an open and crucial question. Older adults, particularly those with other health conditions like diabetes, seem to suffer more from the new coronavirus, accounting for most severe illnesses and deaths, according to the CDC.
SARS killed about 10% of all people it infected -- but roughly half of those over 50, says Vineet Menachery, PhD, an assistant professor at the University of Texas Medical Branch in Galveston whose work is focused on coronavirus vaccines. In those cases, the infected people’s immune systems overreacted, and fluid accumulated in their lungs, he says.
One challenge Moderna had to overcome to develop its new candidate vaccine was figuring out how to engineer its mRNA to get into cells. Zaks says it took the company more than 4 years to engineer an effective mRNA, and it has spent the last 4 or so years beginning tests in people.
Any early trial of a coronavirus vaccine, which Fauci and Zaks say could happen as soon as April, would test the vaccine in about 20 to 25 healthy people, to confirm that it is safe and that it generates a robust immune response. A study like that usually takes about 3 months Fauci says. Assuming good results, a larger study would then be needed.
With SARS, Fauci says, the first-line study showed the candidate vaccine was safe and created an appropriate immune response, “but then the epidemic essentially disappeared,” so it was never needed.
Looking Past the Immediate Crisis
That lack of follow-through frustrates Peter Hotez, MD, the dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston, and co-director of the Texas Children’s Hospital Center for Vaccine Development.
If it had been fully developed then, it might work now against the new coronavirus, but there was no money to bring it to market. “After we manufactured it, we couldn’t get funding to move it into clinical trials,” he says.
“I liken it to a little kids’ soccer game: Everybody runs after the ball, and nobody stays behind to play defense,” Hotez says. “That’s unfortunately the situation we’re in.”
It’s short-sighted, he says, to worry about the price of developing a vaccine, when an epidemic like the current one in China costs orders of magnitude more. “If we had gotten that very modest investment, we would have had a vaccine ready to go,” he says.
“We’ve now had major coronavirus [outbreak] every decade of this 21st century,” Hotez says, with SARS in the 2000s and Middle East respiratory virus, or MERS, which has infected nearly 2,500 people, and killed more than 850 since 2012. “We’ve got to start taking a coronavirus vaccine seriously and putting in infrastructure to start making them.”
No treatment has been proven effective against the new virus, though several developed to treat SARS are now being tested to see if they might also help, Fauci says.
Until a safe, effective vaccine can be developed, the best protection remains hand-washing, says Jeanne Marrazzo, MD, director of the Division of Infectious Diseases at the University of Alabama at Birmingham.
“Hand hygiene cannot be overemphasized,” she says. “I don’t think people need to be shaking hands at this point.” The CDC recommends hand-washing, scrubbing hands for at least 20 seconds after lathering -- about the length of time it takes to sing the “Happy Birthday” song.
Also, she notes, if you get respiratory symptoms, you’re still much more likely to have the “garden variety” flu than the new coronavirus. The flu kills tens of thousands of Americans a year -- including 54 children so far this season. The flu vaccine has been proven safe and generally effective.
The bottom line, Marrazzo says, is though a vaccine against the new coronavirus is still a ways off, there has been some progress.
“It’s kind of encouraging to point out that investments in vaccine technology have come a hugely long way since SARS,” she says.