The search for more effective vaccines

The coronavirus that causes COVID is mutating rapidly and evading immune defenses. Can vaccines keep up?

(Image credit: CHANDAN KHANNA/AFP via Getty Images)

The coronavirus that causes COVID is mutating rapidly and evading immune defenses. Can vaccines keep up? Here's everything you need to know:

Are COVID vaccines still effective?

Without question, but vaccines aren't producing the ironclad immune defense they did initially. Unvaccinated people are still about five times more likely to catch COVID, seven times more likely to be hospitalized, and roughly 14 times more likely to die, according to new data from the Mayo Clinic. But the hypercontagious BA.5 subvariant of Omicron, now the dominant strain in the U.S., is four times more resistant to COVID vaccines than the original Omicron variant, and breakthrough infections have become commonplace. Effectiveness against hospitalization is dropping over time, especially among people over 65 and the immunocompromised. As a result, the Biden administration scrapped plans for a summer booster campaign and instructed Pfizer and Moderna to tailor boosters to BA.4 and BA.5, and those tweaked vaccines are expected as early as mid-September. The White House also recently convened scientists who are pursuing two potential game changers: an inhalable nasal vaccine that could dramatically curb transmission and a universal coronavirus vaccine that could protect against all variants. "Ultimately, we need vaccines that can protect us no matter what Mother Nature throws at us," White House COVID response coordinator Dr. Ashish Jha said.

Why is vaccine efficacy fading?

COVID is constantly evolving, and BA.5 has changed dramatically from the "wild-type" strain that first emerged in Wuhan, China. Pfizer's and Moderna's vaccines train the immune system to target the coronavirus' spike proteins, which latch onto cells. But the spike proteins are one of the fastest-mutating parts of the virus, and the original Omicron variant featured dozens of spike protein mutations. For people who'd received two vaccine doses but no booster, vaccination effectiveness against hospitalization fell to 61 percent, the Centers for Disease Control found, and against Omicron subvariants, the effectiveness rate dropped to 24 percent. Moderna needs about six months to test and develop variant-specific vaccines, and new variants have emerged during the pandemic roughly every four to six months. The result is a frustrating game of whack-a-mole. Many people are getting COVID twice or three times — sometimes just weeks or months apart. New infections in the U.S. may be running at more than 750,000 a day; there are about 3,000 deaths a week, or 150,000 a year, and those numbers may surge in the fall and winter.

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What's the solution?

Scientists have high hopes for nasal spray boosters, which could be key to limiting infections. The current mRNA-based vaccines, injected into a muscle, induce strong immunity in the blood, preventing severe illness, but appear to cause a more limited immune response in the airways where the virus enters the body. A nasal vaccine could stimulate an immune response in the mucosa — the tube lining that runs from the nose and mouth to the lungs and stomach. Nine existing vaccines work along these lines, using oral drops to protect the mucosa against diseases such as polio and the flu. More than a dozen COVID nasal sprays are being developed worldwide, and animal tests show promise. "The hope is to shore up defenses in the nose so that the virus can't replicate in the nose," said Dr. Ellen Foxman, an immunobiologist at the Yale School of Medicine. "That would be like the holy grail."

Is a vaccine against all variants possible?

Dozens of vaccine developers think so. The most ambitious of these universal coronavirus vaccines would target commonalities across the coronavirus family, providing long-term protection against COVID, future variants, and strains in bats and other animals that could jump to humans and cause future pandemics. Researchers at the California Institute of Technology and the University of Oxford produced a vaccine containing parts of spike receptors from eight coronaviruses, including COVID, MERS, and SARS. In monkeys and mice, the vaccine provided broad protection. Another pan-coronavirus vaccine developed by Army researchers has entered Phase I human trials. But full clinical trials could take several years, and there's no guarantee these ambitious vaccines will work.

What's slowed vaccine progress?

"The sense of urgency is completely gone," says Dr. Florian Krammer, a virologist at the Icahn School of Medicine in New York City. Starting in 2020, Operation Warp Speed spent $18 billion to help scientists and pharmaceutical companies accelerate development of COVID vaccines, which were produced in just a year. Federal funding for new vaccines is less than $50 million, and Republicans in Congress have blocked additional COVID funding all year. Vaccine developers say they're struggling to find appropriate volunteers for trials, and there's even a shortage of monkeys and mice for testing. "From day one of this pandemic, we have never tried to get ahead of the virus," said Dr. Eric Topol, director of the Scripps Research Translational Institute. "The initial success of Pfizer's vaccine was 95 percent against symptomatic COVID," Topol said. "This virus is vulnerable. We've proven that. We're just not building on our successes."

A lagging booster campaign

Boosters make a big difference: The CDC found that for Americans older than 50 who received their second booster shot, vaccines were 80 percent effective at preventing hospitalization against the Omicron subvariants, a dramatic improvement. This spring, people above age 50 who'd received just one booster shot were dying from COVID at four times the rate of those who'd received two shots. But three-­quarters of Amer­i­cans eligible for a second booster still haven't gotten one, and more than half of Amer­i­cans haven't received their first booster shot. With cases expected to rise as temperatures cool this fall, the White House says there aren't enough booster doses for every Amer­i­can if eligibility for a fourth shot is expanded to everyone older than 12, as predicted. With the Biden administration's decision to delay the booster push until ­variant-­specific shots are available, some eligible people wonder if they should wait for their fourth shot. "Definitely get it now!" said Paula Cannon, a professor of immunology at the University of Southern California. "Trying to predict the future with this virus, even as close as the fall, is not a good idea."

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