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I’m not sure I’ve read a phrase more often over the past two months than “until there’s a vaccine.”
We are now preparing to take small steps toward our old lives. We’re letting some businesses reopen, allowing people to return to state and national parks, and more — but we are also starting to accept that the coronavirus won’t be eliminated anytime soon.
Until there’s a vaccine, our world will be different.
Face masks will become ubiquitous, indoor sports arenas and big theaters will likely stay closed, and dozens of businesses will be limited, leaving many out of work. That’s the impact for the healthy.
Until there’s a vaccine, those who are elderly or have preexisting conditions will live vastly limited lives or be in significant danger. Remember how obesity was the condition with the strongest tie to critical illness in coronavirus patients in New York City? Well, 42.2% of American adults are obese. And about one in seven Americans, 15.2%, are over age 65.
You’ve probably heard that a vaccine is 12 to 18 months away, but is that really true? Also, how do they work? How do we test them? Can we speed up the process? And what can we do in the meantime?
We all have a stake in this, so let’s try to answer these vital questions.
How do vaccines work?
Vaccines are cool. Essentially, a vaccine is a substance that to the body’s immune system appears like a disease-causing microorganism, like a bacteria or virus. When you inject someone with the vaccine, the immune system learns about the form of the microorganism, then remembers it. That way, the body can immediately kill the microorganism whenever it encounters it in the future, without being fooled or caught off guard in the early stages of infection.
There are a bunch of different ways to make something look like a specific microorganism. The simplest way is to just take some of the disease-causing germ and kill it with heat or chemicals — those vaccines are called inactivated vaccines, and that’s how the polio vaccine works. Another way is to use a particularly weak or even harmless version of the virus — those are called live-attenuated vaccines. This is how the measles vaccine works.
We eventually realized that, in some cases, you could just take part of the microorganism, combine it with something safe, and inject that. Those are called subunit vaccines, and there are a whole bunch of different types. Vaccines for hepatitis, tetanus, and HPV are examples of subunit vaccines.
In the past 20 years, we’ve been working on DNA and RNA vaccines. You’ve probably heard of DNA — it’s the genetic code in your cells, the set of instructions that makes you, you. RNA is essential in turning the DNA code into the proteins that make everything happen in your body. By injecting this DNA or RNA into someone, we can warn the immune system about this code, and have it fight off anything with that code in the future. It should also provide real advantages in terms of production and safety.
DNA and RNA vaccines are new, though: There are no approved DNA or RNA vaccines for human use in the United States. We’ve gotten close with SARS in 2003, bird flu in 2005, swine flu in 2009, and Zika in 2016. We’ve even done trials on an HIV vaccine with these methods.
We also haven’t ever made a vaccine for any coronavirus. Again, we’ve gotten close with SARS and MERS, so scientists are optimistic. But because funding seems to dry up for vaccines late in the process, we haven’t gotten across the finish line, and we’re starting a bit behind. This is one failure of our worldwide health care system.
How are vaccines tested?
Once scientists get a good idea for a vaccine, they’re widely tested in animals in the preclinical stage, looking at whether it works and what dose works best. Testing on mice is common, but this coronavirus doesn’t grow in mice. Testing on an animal more similar to humans, like rhesus macaque monkeys, gives us a better idea.
Then we move to a three-phase process. Phase I studies are done on a small number of volunteers to see how effective the vaccine is in humans and whether it is safe. These volunteers are closely monitored. Phase II studies are larger and consist of several hundred people. Here, safety, effectiveness, dosage, delivery method, and delivery schedule are tested.
Finally, Phase III is the largest study — thousands or tens of thousands of volunteers are used in a study that is randomized, double-blind, with a control group and everything. The vaccine maker is looking for rare side effects at this point.
If everything goes well and is approved by the FDA, vaccine production can start. From 2006 to 2015, only about 16% of vaccines made it from Phase I to approval, 24% from Phase II to approval, and 76% from Phase III to approval. Keep that in mind.
Can we fast-track vaccines?
This whole process usually takes five to 10 years. In the case of this coronavirus, we’re trying to get it done in 12 to 18 months… or faster.
There are things we can do to speed up the process. One is to work in parallel — to, for example, create vaccine production systems even before the tests are complete. That way, we’re not wasting time on construction. Microsoft founder Bill Gates is at the head of some of these efforts.
Another is challenge testing. Normally, vaccine studies involve giving a volunteer a vaccine, then allowing the person to be exposed — or not — to the virus naturally. There are a whole lot of participants who don’t end up getting exposed, making them kind of worthless for the experiment. This means experiments need more people and take more time.
But in this pandemic, every extra day means thousands of additional people die worldwide. So instead, “challenge testing” actually exposes volunteers to the virus in a lab, allowing researchers to find out much more quickly if a vaccine works. It’s normally considered unethical, but many are arguing that challenge testing would save huge numbers of lives. And the coronavirus might be a relatively good candidate for challenge testing anyway: because young people die so rarely from the disease, there’s a natural body of challengees.
That’s the idea behind an organization called 1DaySooner, which is putting together a list of volunteers willing to be infected to advance vaccine development. So far, more than 4,000 people have signed up.
What vaccines are being tested now?
As of April 8, there were 115 vaccine candidates in process, according to Nature. Seven of those had made it to human testing. Here is a look at their status, with major help from Science magazine’s Derek Lowe. (Note: He is not the former Red Sox pitcher.)
Oxford University’s “ChAdOx1-nCov19” vaccine is a DNA vaccine which worked well in monkeys. Researchers are combining their Phase I and Phase II into one large study with multiple “endpoints,” or places the study can stop if things go poorly. They’re saying their Phase III testing could start “at the end of next month,” and if that goes well, they could have a few million doses of their vaccine by September. Wow.
Both the U.K. and the Netherlands have started manufacturing plants for this vaccine in case testing goes well, spending millions of dollars. However, there isn’t yet a North American manufacturing partner. If our government wants to speed up vaccine production, spending money on this one seems like a worthwhile gamble.
CanSino Bio’s “Ad5-nCoV” vaccine out of China also uses the DNA method. Researchers advanced it to Phase II already, based on preliminary results in Phase I testing. The vaccine worked well on monkeys, but the company hasn’t made the results of early human testing public yet.
As Lowe notes of the two Phase II candidates, “there is literally no way to know which of these competing efforts will yield a better vaccine, or if either will work at all”
U.S.-based Moderna’s mRNA1273 vaccine is an RNA vaccine that is currently in Phase I, with Phase II slated for “second quarter 2020.” The Phase I testing includes two injections, with a second shot being administered about a month after the first. That second shot was just given last week to volunteers in Seattle and Atlanta.
Philadelphia-based Inovio’s INO-4800 vaccine is a DNA vaccine that began Phase I testing on 40 patients in April. The fun quirk about this one is that it uses a new method called a “Prickly Patch” to deliver the vaccine: It’s a fingertip-sized patch with teensy pointers made of sugar and the vaccine. You put it on your skin, and the moisture from your skin dissolves the sugar and delivers the vaccine to your skin cells. It propagates through your body from there.
Germany’s BioNTech and U.S.-based Pfizer are teaming up to test four different RNA vaccines at once. They’ve also received clearance to do a combined Phase I/II trial at the same time with these vaccines, which has started in Germany and could start in the U.S. next week with federal approval. They say they could produce “millions” of doses by the end of 2020 if things go well, and “hundreds of millions” in 2021.
China-based Sinovac’s PiCoVacc vaccine is an old-school inactivated virus vaccine, which also will probably need a booster. But a simple approach may prove effective and has had encouraging results in monkey testing with this coronavirus. It has been approved for human testing.
The Wuhan Institute of Biological Products is also making an inactivated-virus vaccine, but there’s little public information available.
Remember: It is likely that most of these candidates will fail, but it’s good that we’re trying multiple approaches with multiple delivery systems. A first vaccine will “win the race,” but creating many successful vaccines may allow us to get more doses to more people faster. Variety also gives us the advantage of using the best vaccine for each use-case.
Given that the U.S. hasn’t found a manufacturing partner for the Oxford vaccine, which seems to be furthest along, I’d say the fourth quarter of 2020 or the first quarter of 2021 are the best-case scenarios for actually being able to use these early vaccine candidates if they are successful. The rollout will take some time, too. Even if millions of doses are produced then, the first to be vaccinated will be health care workers and the most vulnerable.
What do we do until then?
Well, from a scientific point of view, we work on treatments.
One that has had impressive effectiveness in limited trials so far is plasma therapy. This is stupid-simple science: Since recovered COVID-19 patients have immune systems that have created antibodies for the virus, why not just extract some of their blood and put it in sick people? That way they’ll have the antibodies, too! This has been used since the 1800s.
Cynthia Lemus, a 24-year-old flight attendant from Magna, was the first person in Utah to be treated in this way by Intermountain Healthcare about a week ago.
The problem is that plasma is pretty variable depending on the source, and that can mean “good batches” and “bad batches” of plasma. Blood plasma transfusions can also result in some nasty side effects, like allergic reactions to the plasma given. There may not be much plasma available in the early days of an up-swinging pandemic. And finally, these antibodies don’t provide immunity; someone could still be infected again down the road.
There are hundreds of studies underway on plasma therapy and other treatments. Until there’s a vaccine, they are our best shot at saving lives.
Ah, there’s that phrase again. “Until there’s a vaccine” — a reminder of a future where our lives return to normal, a reminder we’re still so far away.