In a medical research project nearly unrivaled in its ambition and scope, volunteers worldwide are rolling up their sleeves to receive experimental vaccines against the coronavirus — only months after the virus was identified.
Companies like Inovio and Pfizer have begun early tests of candidates in people to determine whether their vaccines are safe. Researchers at the University of Oxford in England are testing vaccines in human subjects, too, and say they could have a one ready for emergency use as soon as September.
The findings will pave the way to development of a human vaccine, said the investigators. They have already partnered with Janssen, a division of Johnson and Johnson.
In labs around the world, there is now cautious optimism that a coronavirus vaccine, and perhaps more than one, will be ready sometime next year.
Scientists are exploring not just one approach to creating the vaccine, but at least four. So great is the urgency that they are combining trial phases and shortening a process that usually takes years, sometimes more than a decade.
“It’s an easier target, which is terrific news,” said Michael Farzan, a virologist at Scripps Research in Jupiter, Fla.
“What people don’t realize is that normally vaccine development takes many years, sometimes decades,” said Dr. Dan Barouch, a virologist at Beth Israel Deaconess Medical Center in Boston who led the monkey trials. “And so trying to compress the whole vaccine process into 12 to 18 months is really unheard of.”
“If that happens, it will be the fastest vaccine development program ever in history.”
More than one hundred research teams around the world are taking aim at the virus from multiple angles.
Moderna’s vaccine is based on a relatively new mRNA technology that delivers bits of the virus’s genes into human cells. The goal is for cells to begin making a viral protein that the immune system recognizes as foreign. The body builds defenses against that protein, priming itself to attack if the actual coronavirus invades.
Some vaccine makers, including Inovio, are developing vaccines based on DNA variations of this approach.
But the technology used by both companies has never produced a vaccine approved for clinical use, let alone one that can be made in industrial quantities. Moderna was criticized for making rosy predictions, based on a handful of patients, without providing any scientific data.
Other research teams have turned to more traditional strategies.
Some scientists are using harmless viruses to deliver coronavirus genes into cells, forcing them to produce proteins that may teach the immune system to watch out for the coronavirus. CanSino Biologics, a company in China, has begun human testing of a coronavirus vaccine that relies on this approach, as has the University of Oxford team.
Other traditional approaches rely on fragments of a coronavirus protein to make a vaccine, while some use killed, or inactivated, versions of the whole coronavirus. In China, such vaccines have already entered human trials.
Florian Krammer, a virologist at Icahn School of Medicine at Mount Sinai in New York, predicted that at least 20 additional vaccine candidates will make their way into clinical trials in the weeks to come.
“I’m not worried at all about it,” he said of the prospects for a new vaccine.
Many of these vaccines will stumble as the trials progress. As more people are inoculated, some candidates will fail to protect against the virus, and side effects will become more apparent.
But from what scientists are learning about the coronavirus, it ought to be a relatively easy target.
The coronavirus sports tempting targets on its surface, unique “spike” proteins the pathogen needs to enter human cells. The immune system readily learns to recognize these proteins, it appears, and to attack them, killing the virus.
Viruses can challenge vaccine makers by mutating rapidly, changing shape so that antibodies that work on one viral strain fail on another. Thankfully, the new coronavirus seems to be a slow mutator, and a vaccine that proves effective in trials should work anywhere in the world.
When work on a coronavirus vaccine started, some researchers worried that antibodies actually might worsen Covid-19, the illness caused by the coronavirus. But in early studies, no serious risks have emerged.
“That doesn’t mean that there won’t be, but so far there hasn’t been any indication, so I’m cautiously optimistic on that point,” said Dr. Alyson Kelvin, a researcher at the Canadian Center for Vaccinology and Dalhousie University.
Ensuring that vaccines are safe and effective demands large trials that require careful planning and execution. If successful vaccines emerge from those trials, someone’s going to have to make an awful lot of them.
Almost everyone on the planet is vulnerable to the new coronavirus. Each person may need two doses of a new vaccine to receive protective immunity. That’s 16 billion doses.
“When companies promise of delivering a vaccine in a year or less, I am not sure what stage they are talking about,” said Akiko Iwasaki, an immunobiologist at Yale University. “I doubt they are talking about global distributions in billions of doses.”
Manufacturing vaccines is profoundly more complex than manufacturing, say, shoes or bicycles. Vaccines typically require large vats in which their ingredients are grown, and these have to be maintained in sterile conditions. Also, no factories have ever churned out millions of doses of approved vaccines made with the cutting-edge technology being tested by companies like Inovio and Moderna.
Facilities have sprung up in recent years to make viral-vector vaccines, including a Johnson & Johnson plant in the Netherlands. But meeting pandemic demand would be an enormous challenge. Manufacturers have the most experience mass-producing inactivated vaccines, made with killed viruses, so this type may be the easiest to produce in large quantities.
But there cannot be just one vaccine. If that were to happen, the company that made it would have no chance of meeting the world’s demand.
“The hope is that they will all, at some level, be effective, and certainly that’s important because we need more than just one,” said Emilio Emini, a director of the vaccine program at the Bill and Melinda Gates Foundation, which is providing financial support to many competing vaccine efforts.
As part of a public-private partnership the White House calls Operation Warp Speed, the Trump administration has promised to design a kind of parallel manufacturing track to run alongside the clinical trials, building up capacity well before trials are concluded, in hopes that one or more vaccines could be distributed immediately upon approval.
President Trump said on Friday that the goal of the project was to distribute a vaccine “prior to the end of the year.” To do that, Mr. Trump is relying on the Defense Department to manage the manufacturing logistics related to vaccine development.
But in an interview on Thursday, Gen. Gustave F. Perna, who will manage the manufacturing logistics, said discussions about the equipment and facilities needed for production were just beginning.
He described his work as a “math problem”: how to get 300 million doses of a vaccine that doesn’t yet exist to Americans — by January.
He added: “Now, how am I going to distribute it? What is it going to be distributed in? What do I need to order now to make sure I have the distribution capability? The small bottles, the trucks.”
Dr. Amesh Adalja, an infectious disease physician and senior scholar at the Johns Hopkins University Center for Health Security, said that seemingly minor aspects of production and distribution could complicate progress later on.
“This is on a scale we’ve never seen since the polio vaccine,” he said. “It’s the little things like the syringes, the needles, the glass vials. All of that has to be thought about. You don’t want something that seems so simple to be the bottleneck in your vaccination program.”
A coronavirus vaccine doesn’t yet exist, but already there are questions about who will be able to afford it.
Last week, Oxfam organized an open letter from 140 world leaders and experts calling for a “people’s vaccine,” which would be “made available for all people, in all countries, free of charge.”
“These vaccines have to be a public good,” said Helen Clark, the former president of New Zealand who signed the open letter. “We’re not safe till everyone is safe.”
Sui-Lee Wee contributed reporting from Singapore.