Christopher Pledger / eyevine
En español | One thing is certain: It won’t be just another flu vaccine.
Medical researchers worldwide are working toward a single goal: to develop a vaccine, or vaccines, to protect us from the novel coronavirus and the disease it causes, COVID-19. The crucial puzzle piece? Ensuring it is effective in the most at-risk population — older adults.
As we age, our immune systems become less efficient and, as a result, vaccines are less effective — the 2017–2018 flu vaccine, for example, was 38 percent effective in the general population but less than 20 percent effective in people over 65. So a standard antibody-producing vaccine, while helpful, may not be the preventive resource we need.
Antibodies are key to a second goal, too: finding a treatment that doctors can use to mitigate the worst symptoms and outcomes of the disease when people do get it.
A winding road forward
Once you’re exposed to a virus, a race begins between the virus and the body’s immune system; which one will overwhelm the other? “If we can give the immune system a head start, instead of the body starting from zero, we get it to a stronger position,” says Paul Duprex, director of the Center for Vaccine Research at the University of Pittsburgh. “How do we do that? We expose people to fragments of the virus before the real virus comes along. That is the process of vaccination in the simplest sense.”
Over the past several months, you’ve probably read dozens of stories of promising new vaccines, including trials being conducted on people 50 and older. Anthony Fauci, M.D., our national beacon of medical hope through this crisis, made headlines in early June when he said that we should have “a couple of hundred million doses” of a candidate vaccine by the beginning of 2021.
But here’s the problem with all that news, Duprex says. In a Zoom video call, he holds up a stapled sheaf of papers that has lists and details printed on both sides. “This is the World Health Organization’s master list of candidate vaccines. Look at all these.” He shows me: There are scores, if not hundreds. “These are in clinical development. Only a few have gone to phase one clinical trials. It’s important for your readers to understand: We don’t have a vaccine. Even if it’s in phase one, it’s not a vaccine. It’s a candidate vaccine. It’s not a vaccine until it’s a product. A product of millions and millions of doses. That’s when it matters.”
And that’s why even Fauci can’t say whether all those millions of doses he’s talking about will even be effective. In essence, every scientist in the world is trying to turn a marathon into a sprint. Here’s how that final product, or products, will most likely happen.
Step one: Identify the target
Back in March, researchers from the University of Texas and the National Institutes of Health revealed the first three-dimensional atomic map of the novel coronavirus’ spike protein, the part of the virus that binds to and infects human cells. The spike proteins look exactly as they sound: the spikelike structures we see sticking out of the ubiquitous spherical renderings of the virus.
This spike protein binds to host cells at least 10 times as tightly as the corresponding spike protein of the SARS-2 virus. Mapping this protein is the first step toward a vaccine because the spike is one element of this virus that our body can identify as an enemy. By replicating the spike protein and introducing it to human cells, we’ll trigger an immune response and create antibodies.
“Everybody’s focused on the spike protein, and let’s hope we’re right,” Duprex says. “That’s what the immune system ‘sees’ first. So we introduce the spike into the body; the immune system ‘sees’ the spike and begins to make antibodies that recognize it.
“It’s all about getting that spike protein into a person in a clinical trial and asking: Do we generate antibodies that are ready to neutralize the virus?”
The X factor here is ensuring that this antibody reaction happens robustly in older people. Researchers determine a vaccine’s effectiveness based on the “seroconversion of infection,” a term that refers to your body’s production of detectable levels of an antibody.
If you get to seroconversion in over 95 percent of all vaccinated people, “that’s a great vaccine,” Duprex says. But he says that’s for something like the measles shot; flu shots are much less effective. For the coronavirus? “Who knows if 25, 30 or even 50 percent effectiveness will be enough to protect older people,” he says. “We would love to hit measles-level effectiveness. If you get just over 50 percent in younger, healthy people, that’s like fighting a battle with one leg. If the vaccine doesn’t work as well in older folks — say, 25 percent — it’s like fighting the battle with one and a half of your legs missing.”
That’s why there’s another step to this process.
Step two: Find the add-ins
A little-known fact: Scientists have created extra ingredients they can add to vaccines to make them work better. This is crucial in the quest to make an effective vaccine for older adults whose immune systems are on the decline.
Jay Evans, director of the Center for Translational Medicine at the University of Montana and a leading expert on these ingredients, known as adjuvants and immunostimulants, says they will likely be a key factor in COVID-19 vaccines’ working in older adults.
“We have libraries of compounds that we’ve developed over the last 25 years that target specific immune receptors and drive different types of immune responses,” he says. “We’re starting to look at blood samples collected from people over 60 and screening these same immunostimulants or adjuvants in vaccines in these samples to understand which types they’ll best respond to.”
One key area is using adjuvants to encourage T cells — the body’s virus fighters — to “wake up” and go to work in these populations. This is not an easy trick, Evans says. “If you choose the wrong adjuvant, you could produce a very healthy immune response in someone who’s 30, and something that’s not effective, or potentially damaging, in someone who’s 70.”
This is where the idea of multiple vaccines comes into play — maybe one for a younger population and another with different ingredients for older people.
“It’s plausible that a vaccine that works on people under the age of 2 or someone who’s 20 or 30 might require a different adjuvant for someone over age 60,” Evans says.
Step three: Hedge against failure to find an age-specific vaccine
Science has been successfully creating vaccines for an older population — shingles and pneumonia, for example — but given the compressed time line on this one, no one is sure what will happen. Still, even if no vaccine is found that is effective in older adults — or a vaccine performs in slower or less effective ways, like the flu shot — that doesn’t mean we can’t still triumph over COVID-19.
“Let’s make sure a useful vaccine helps older people, but let’s also quash this thing in younger people so we reduce the overall circulation of the virus,” Duprex says. “That’s what happened with measles. And measles is the most infectious human virus on the planet.”
Step four: Develop a treatment for the sick
Progress has also been made in the other big race: finding an antibody treatment for people who have already been infected.
The key immune cells in a fight with a virus are your T and B cells, two varieties of white blood cells, and that’s where this research focuses, says Lauren Ehrlich, associate professor of molecular biosciences and oncology at the University of Texas at Austin.
And here is where we meet a Belgian llama named Winter, whose blood was used to find a breakthrough in this area. Llamas make antibodies in a way similar to humans, Ehrlich says. By immunizing the llama with the spike protein, scientists were able to generate antibodies against it, and then reproduce them for use in a human medication.
“The antibody therapy could potentially neutralize the spike protein and prevent viral entry,” Ehrlich says. In people who are already infected, this could help reduce symptoms and length of infection.
In search of a time line
In a normal, nonpandemic time line, effective vaccines take years to develop. When you take into consideration breaking down an antigen, producing the right immune response, figuring dosage, and moving into clinical trials and clearing every regulatory hurdle, and then producing a product and bringing it to market, you’re talking three to five years, Evans says. His prediction? “No earlier than fall 2021.”
Fauci’s latest prediction of early next year is far more optimistic, of course. In the end, no one really knows how long it will take to develop vaccines and therapies. But one thing is completely in your control: Get healthier. “The data’s pretty clear on people who are healthy and active and who control their weight,” Evans says. “All those things are associated with better immune response. Not only the better you’ll respond to the vaccine when it’s available, the better you’ll respond if you get the coronavirus.”
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Improving your health could be a very useful summer project, because while all the oxygen goes to COVID-19, Evans reminds us that we have another flu season approaching on top of our coronavirus concerns. “Especially for those over age 60,” he says, “an active lifestyle, eating healthy, sleeping well — all that drives your immune system in the right direction.”
Mike Zimmerman is the author of The 14-Day Anti-Inflammatory Diet.