A year after first COVID-19 vaccine, here's what's next for researchers – and what worries them
The first COVID-19 vaccines were given out a year ago, and more than 450 million shots have since been administered across America. The rapid development and manufacturing has been described as one of the greatest scientific achievements of our time.
With all that progress – not to mention billions of dollars spent on vaccine development – what's next for vaccines?
Researchers are racing to create variant-specific boosters, the first of which could be available as soon as March. Scientists are also working on vaccines that will act against a broader range of variants and viruses, as well as ways to preserve doses so they will be hardier and won't require freezing.
In the future, shots may go away altogether, replaced by nasal sprays and microneedles that go on like Band-Aids. One experimental vaccine, which is just beginning testing in people, delivers its "shot" with a burst of air.
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But experts agree the main focus of the next year won't be new technologies, but simply getting vaccines into arms. More variants will continue to emerge until global spread can be slowed by getting the vast majority of the world's 7.9 billion inhabitants protected.
"It is more and more important to have vaccines out to as many people as possible," said Dr. Sanjeet Singh Dadwal, chief of the Division of Infectious Diseases at City of Hope Comprehensive Cancer Center, in Duarte, California.
Roughly 80 million to 90 million Americans remain unvaccinated, noted Dr. James Hildreth, president and CEO of Meharry Medical College in Nashville, Tennessee, and far more across the world haven't had access to shots.
"This is not over," Hildreth said. "So many people acting as if it's over is just going to facilitate another surge and another."
How current vaccines might change
Vaccine makers already are scurrying to develop shots that target the omicron variant. BioNTech's CEO said his company can have one ready in about three months, pending regulatory approval.
Vaccines may still be effective enough against omicron, experts said. But the virus will continue to evolve as it spreads, leaving people vulnerable to a version of the virus that can't be controlled by current vaccines, said Dr. Barton Haynes, a leading vaccine researcher at the Duke University School of Medicine in Durham, North Carolina.
"If it isn't omicron, it'll be tau or zeta or whatever," he said.
Haynes and his colleagues are working to develop a vaccine able to control any variant that might pop up over the next five years. "It is critical to the ultimate control of the pandemic, particularly if we can get something out in the next year," he said. "I'm optimistic that we have a good shot at it."
But even if a variant-specific vaccine can be made at record-breaking pace, another new variant will likely have taken over by the time shots can be delivered, said Dr. Salim Abdool Karim, a South African clinical infectious diseases epidemiologist.
Delta, for instance, first appeared early this year in India and now looks like it's going to be replaced by omicron.
"That's not enough (time) to make a new vaccine and to vaccinate the whole population. Can't do it," Karim told a group of 200 Harvard researchers in a video call last week. "We are going to have to make something that's much broader in terms of immune responses anticipating what future variants might look like."
New vaccine technologies
Vaccines from Moderna and Pfizer-BioNTech are based on a new technology called mRNA.
"The RNA vaccines have set such a high bar," said Dr. Warner Greene, a virologist and immunologist at the Gladstone Institutes, an independent, nonprofit life science research organization in the San Francisco Bay Area.
But not an insurmountable one. "If someone can come up with a vaccine that is far more durable while retaining the same properties of high efficacy, that could be like delta pushing all the other variants out – that vaccine could push out the RNA vaccines," he said.
Current vaccines could be improved by reducing their need to be frozen, added his colleague Dr. Melanie Ott, director of the Gladstone Institute of Virology, speaking on the same recent conference call with media.
Several large companies are still trying to bring vaccines to market, along with a number of small biotechs.
Novavax, which received nearly $1 billion in federal funds and conducted large, promising clinical trials, recently received authorization to provide its vaccine in the Philippines and Indonesia, and hopes to offer it around the globe in the coming year.
The company has said manufacturing challenges slowed it down. Scaling up production to hundreds of millions of doses has been a bigger hurdle for many companies than simply designing an effective vaccine.
Other new COVID-19 vaccines in the works include:
GlaxoSmithKlineannounced this month that it has paired with a Canadian biotech firm Medicago to develop the first COVID-19 vaccine candidate made in plants. In a large trial of 24,000 adults, the companies showed their vaccine was 75% effective at preventing sickness from the delta variant. All trial participants who suffered severe disease had received a placebo.
Dadwal and his colleagues at City of Hope have teamed up with Georgia biotech GeoVax to develop a vaccine aimed at people with weakened immunity, who can't mount a strong response to the current vaccines. It's currently been tested in a 250-person trial and aims at both the spike protein that all the other vaccines target, as well as other parts of the virus. Because of that, Dadwal said, he hopes their vaccine will fare better against a wide range of variants.
Gritstone Bio, based in Emeryville, California, is focusing on generating T cells, the body's long-lasting response to infections. Most vaccine-makers say their shots generate T cells, but Gritstone's president and CEO Dr. Andrew Allen said he thinks his will generate more. "This whole concept (is) that T cell immunity is what keeps you well even when you get exposed to this virus," he said.
Gritstone and Novavax have contracts to provide vaccines to low- and middle-income countries through the Coalition for Epidemic Preparedness Innovations, or CEPI.
Uvax Bio, of Wilmington, Delaware, has developed a vaccine that looks to the immune system almost exactly like SARS-CoV-2 – "really nice-looking protein balls with spikes on the surface, almost like the virus, but it's pure protein, so it's safe," said Jiang Zhu, a company co-founder and structural biologist at The Scripps Research Institute in La Jolla, California.
An ongoing trial is testing the company's vaccine as a booster for people who've already received commonly available shots, hoping the combination of technologies will provide better, longer lasting protection, said Dr. Cheryl Keech, Uvax Bio's acting chief medical officer.
Lab studies conducted before the arrival of omicron showed it triggered a strong response to a wide range of variants. Zhu said he thinks it will work against omicron, too.
"If we had this vaccine now, we would be able to stop the spread almost immediately," he said.
Calling all coronaviruses
Researchers are worried the next coronavirus could be as hard to contain as the current pandemic and as lethal as the two coronaviruses that spread earlier this century, SARS and MERS, which killed 10% to 30% of those infected. So scientists hope to develop a vaccine that could be stockpiled in advance of a novel coronavirus.
Covering all the variations between MERS, SARS and SARS-CoV-2 will be tough in a single vaccine, though, Haynes said.
The broader the vaccine, the longer it will take to develop, said Dr. Duane Wesemann, an immunologist at Brigham and Women's Hospital in Boston, who like Haynes, recently received a federal grant to develop a vaccine against a range of coronaviruses.
"That's been much more difficult than it seems on the surface," Wesemann said. "We need to learn more about the immune system itself, in addition to trial-error engineering."
Wesemann said he thinks this and other problems can be overcome. The open question, he said, is how long it will take.
"We'll find a solution, a way to develop strategies that will work, I'm confident that's going to happen," he said. "Whether that's going to happen in 20 years or in 2 years I'm less certain."
Vaccines don't save lives, vaccinations do
The challenge over the next year will be getting more shots in arms – in the U.S. and elsewhere, said Hildreth, who has studied viruses for decades and also sits on a federal advisory panel that reviews vaccines. "They can't just be vials sitting on a shelf."
Some Americans have dug in and said they're unwilling under any circumstances to get a COVID-19 vaccine. Hildreth said he'd like to focus "on those willing to listen," reaching out with trusted information sources to talk about the importance of vaccination.
New vaccine technologies are great, he said, but they have to be paired with public education. "We have to increase the health literacy so people understand why vaccines are effective at preventing disease and why that's so important."
The U.S. and other wealthy countries also have to do a better job of distributing vaccines around the world, he and others said.
Dr. Rebecca Weintraub, an assistant professor of Global Health at Harvard Medical School, said more countries need infrastructure to manufacture vaccines themselves. "That decreases transportation requirements and adds technical capacity in areas of the world," she said.
Data collection has to get better, too, Weintraub said. The United States lacks a centralized system tracking the speed of a viral variant and ensuring the equitable distribution of vaccines.
That will become increasingly important as the virus gets better at evading vaccines and protection from previous infection, Hildreth said.
Preserving vaccine effectiveness requires the vast majority of people to be fully protected – to limit the opportunities the virus has to mutate, especially in those who have weak immune systems and can't easily fight off the virus, he said.
Since not everyone can get full protection from vaccines, other means of helping people avoid severe illness will become more important.
This year was the year of "vaccines, vaccines, vaccines," said Karim, the South African scientist. "The next era is going to be an era of treatment."
Contact Karen Weintraub at firstname.lastname@example.org.
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