This week has been a tough one for Americans, as the U.S. started to grapple with the full brunt of the ongoing COVID-19 pandemic. There was one bright spot, however. On Monday, researchers in Seattle injected the very first patients with a possible COVID-19 vaccine.
At the Kaiser Permanente Washington Research Institute in Seattle, the first clinical trial for a COVID-19 vaccine is now underway. Eventually, 45 healthy volunteers will receive two shots of the vaccine, one month apart, to test the safety and antibody response from the vaccine, according to a statement Kaiser Permanente provided to Discover.
This vaccine, along with many others being developed in the U.S. and around the world, works by targeting the spikey, crownlike protein that gives coronaviruses the “corona” in their name. The clinical trial in Seattle marks the beginning of the lengthier stage of vaccine development: testing. Researchers are hopeful that, within a year or 18 months, this vaccine — or one of the others currently being developed — will deploy cutting-edge science to protect millions of people around the world from the disease currently remaking life as we know it.
“This has been an accelerated timeline, which we see as a positive given we are in the middle of a pandemic,” says Kathleen Neuzil, director of the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health.
Targeting the Crown
Coronaviruses, like the one that causes COVID-19, use their namesake spikes to penetrate a normal cell inside the airway or lungs. Once the virus has entered the cell, it takes over the cell’s machinery and uses it to churn out more copies of the virus that will infect other cells nearby.
During this process, the spike protein changes shape many times. “If you think of it as a mushroom, the cap comes off and the stalk rearranges and shoots part of itself into the host cell membrane, then wraps around and fuses together, and at that point the cell becomes infected,” explains Jason McLellan, a molecular biologist at the University of Texas at Austin who has studied other coronaviruses.
The vaccine being tested in Seattle, officially named mRNA-1273, essentially trains the immune system to recognize the unique shape of these mushroomlike spikes when they first enter the body, says McLellan. Unlike many vaccines, this one does not contain the virus itself, so it cannot cause illness. Instead, the vaccine is made with snippets of the coronavirus’s genetic sequence.
The pieces of genetic code are encased in “information molecules” called messenger RNA. When these molecules are injected into cells in the human body, the cells read the genetic sequence inside and start generating spike proteins that match the shape of those of the coronavirus when it first enters the body.
The immune system will then recognize these proteins as foreign invaders and create antibodies that bind to the harmless spikes. If it works, when the real virus comes along these antibodies will be ready to bind with the actual coronavirus spike protein, blocking the virus before it invades any cells. “Your body can make antibodies against anything, and we want the antibodies your body makes to be neutralizing — and, by neutralizing, I mean can block infection,” says McLellan.
Many other vaccines currently being developed use a similar strategy, he says, although some target specific parts of the spike protein rather than the whole thing. But if the virus starts to change or mutate over time, a more targeted vaccine may lose its efficacy, he says.
Moves Fast but Feels Slow
Even if things go well with vaccine testing, it will takeabout a year to 18 months to have a vaccine ready for public consumption, according to Anthony Fauci of the National Institute of Allergy and Infectious Diseases. To many of us adjusting to a life of social distancing, that feels like an impossibly long time. But given that this virus was identified for the first time three months ago, this is vaccine development at warp speed.
For example, scientists in China released the genetic sequence for SARS-CoV2 — the formal name given to the coronavirus strain responsible for COVID-19 — in January. By mid-February, McLellan and his team had mapped the three-dimensional shape of these spikes and published the structures in the journal Science. McLellan’s longtime collaborator at the National Institute of Allergy and Infectious Diseases, Barney Graham, worked with the biotechnology company Moderna Inc. to use those structural studies to develop the vaccine now being tested in Seattle.
A few factors have helped accelerate the timeline for developing COVID-19 vaccines, says Neuzil. Manufacturers have been able to follow the same process they would for, say, an influenza vaccine, and swap in coronavirus genetic code for influenza genetic code. “That is one way to fast-track,” she says. Scientists like McLellan are also able to apply research done on other coronaviruses and their vaccines to the search for an effective SARS-CoV2 vaccine.
But the most time-consuming part of the process for all of the COVID-19 vaccines being developed still lies ahead. “The longest part is not making the vaccine, it’s clinically demonstrating it actually works,” says Anastasia Khvorova, a professor with the RNA Therapeutics Institute at the University of Massachusetts Medical School. Researchers have to try the vaccine in tens, then hundreds, and then thousands of people to make sure it is both safe and effective, says McLellan. The trial currently underway in Seattle is the first of three and is expected to take 14 months.
“Because vaccines are given to healthy populations, we have a very high bar for safety,” says Neuzil.
Dozens of other companies, organizations, and government agencies are also reportedly working on developing a COVID-19 vaccine. Many use the genetic sequence approach, while others are trying the traditional live-virus approach.
The RNA-based vaccines like the one in Seattle may have an advantage when it comes to manufacturing, says Khvorova. Live-virus vaccines take time to produce, as the virus has to be methodologically weakened before it is ready to be injected into humans. But this genetic sequence technique requires no such lag time, she says.
Until there is a vaccine or treatment for COVID-19, social distancing will likely remain a key part of our public health strategy. Here’s to hoping the quest for a vaccine continues at a speedy clip.