COVID-19 vaccines delivered as nasal sprays rather than injections are in development by at least nine labs and companies around the world, according to the World Health Organization.
Besides being less uncomfortable than a needle in the arm, these vaccines also may do a better job than injected vaccines at stopping the COVID-19 coronavirus where it first enters the body.
And by keeping the virus from breeding in our noses and throats, nasal vaccines may also do a better job of stopping it from spreading from person to person. That's especially important with the omicron variant, which is spreading like an oil slick.
Most of these vaccines are in early- or middle-stage testing, so it's not clear when or if any will be available. One has dropped out.
But scientists in the United States, China, Cuba, Iran and elsewhere are forging ahead.
"I'm optimistic that there could be a contribution for this type of vaccine in the pandemic, especially at the tail end of it," said Michael Diamond, immunology professor at Washington University in St. Louis.
While the current COVID-19 vaccines have done a great job of preparing most of our immune defenses, they have one major blind spot: our noses, throats and other mucous membranes, where our insides meet the outside world.
Mucous membranes harbor a different kind of antibodies from those circulating in our blood. Injected vaccines delivered into the arm muscle only reach the blood. They don't do much to produce mucosal antibodies.
"Because you taught your immune system how to recognize (the virus) from your muscles, your immune system had no idea that it needed to also protect against (it) in your mucosa," New York University immunology professor Ben tenOever said.
Vaccines sprayed in the nose aim to fight the virus at its first point of contact.
"You're ready for it because you have the immunity right at the spot where you need it," Diamond said.
Diamond and colleagues developed a nasal COVID-19 vaccine and licensed it to Indian pharmaceutical company Bharat Biotech. The company is set to begin the final, large-scale clinical trials needed for regulatory approval.
The fact that injected vaccines don't produce much mucosal immunity would help explain why breakthrough infections from omicron have been common but usually not serious.
"We have very little immunity in the upper airway, which is why people getting infected very commonly are having upper respiratory symptoms" including a cough, sore throat, runny nose or congestion, Diamond said.
"But the vast majority of people are not getting severe disease because they still have this systemic level of protection."
As long as our noses and throats harbor the virus, we can spread it easily, even if we don't know we're infected. That's a big problem with COVID-19. An effective nasal vaccine could help solve it, said Ursula Buchholz, chief of the RNA viruses section at the National Institute of Allergy and Infectious Diseases (NIAID).
"Even nonsymptomatic individuals would not be at risk of shedding virus" if protection was good enough, she said.
Buchholz and colleagues are developing a nasal COVID-19 vaccine designed for children. In animal tests, it did better than an injected vaccine at stopping the virus. The vaccine is starting early-stage clinical trials. Buchholz didn't want to speculate about how soon it might be available.
One other nasal vaccine has already failed. In an early clinical trial, the vaccine from pharmaceutical company Altimmune produced a lower immune response than the shots already on the market. The company pulled the plug last June.
Others see nasal vaccines as a promising way to deliver booster doses.
That's partly because half the world's population is vaccinated already but needs boosters to keep up with variants.
Also, it's just much harder at this point in the pandemic to find people who have not already been vaccinated or infected and who want to help test a vaccine.
"The people who are willing to get vaccinated probably have been vaccinated," Diamond said. "Those who are not willing are not going to go into your trial. So, you run into this little conundrum."