Vaccines inhaled through the mouth or nose might stop the coronavirus in its tracks, although there’s little evidence from human trials so far.
By Emily Waltz
Editor’s note: Indian regulators approved Bharat Biotech’s intranasal vaccine for emergency use on 6 September.
Are sprays the future of COVID-19 vaccines?
That’s the hope of dozens of research groups and companies working on new kinds of inoculation. Rather than relying on injections, these use sprays or drops administered through the nose or mouth that aim to improve protection against the virus SARS-CoV-2.
It’s one of more than 100 oral or nasal vaccines in development around the world. In theory, these vaccines could prime immune cells in the thin mucous membranes that line cavities in the nose and mouth where SARS-CoV-2 enters the body, and quickly stop the virus in its tracks — before it spreads. Vaccine developers hope that these ‘mucosal’ vaccines will prevent even mild cases of illness and block transmission to other people, achieving what’s known as sterilizing immunity. A few mucosal vaccines are already approved for other diseases, including a sprayable vaccine against influenza.
Evidence in animals supports the idea that sterilizing immunity can be induced against COVID-19, although data from humans are scant. Nature explains why mucosal vaccines might help to quash SARS-CoV-2, and what the latest findings mean.
Why might mucosal vaccines be better than conventional shots?
The COVID-19 vaccines currently in use do a good job of reducing disease severity and preventing hospitalization, but don’t block mild illness or transmission that well.
One reason is that they are injected into muscle. Intramuscular shots prompt an immune response that includes T cells, which destroy infected cells, and B cells, which produce antibodies that ‘neutralize’ pathogens — binding to them to stop them entering healthy cells. These cells and antibodies circulate through the bloodstream. But they aren’t present at high enough levels in the nose and lungs to provide rapid protection. In the time it takes for them to journey there from the bloodstream, the virus spreads, and the infected person gets ill.
Mucosal vaccines can prompt a whole-body immune response, but they can also activate immune cells in the mucosal tissue of the nose and respiratory tract. These localized cells “act as sentinels at the site of infection”, says Benjamin Goldman-Israelow, a physician-scientist at Yale School of Medicine in New Haven, Connecticut. “They can act much more quickly.”
The localized mucosal immune cells, known as tissue-resident memory T and B cells, have slightly different functions from the circulating T cells and B cells. For instance, tissue-resident memory B cells produce antibodies called secretory immunoglobulin A (IgA), which are intertwined with the layers of the respiratory tract, where they might be able to stop pathogens quickly. However, it is unclear how well secretory IgA will protect against SARS-CoV-2.
Researchers are testing mucosal vaccines as first doses for unvaccinated people and as boosters for those who have already received COVID-19 shots. Some mucosal vaccines are identical to injected vaccines, but are squirted as liquid or droplets up the nose. Others have a different composition, or are prepared differently. For instance, the mucosal vaccine developed by CanSino is the same as its injected one, but is packaged into aerosols and inhaled through the mouth with a nebulizer at one-fifth the dose of the injected version. A few mucosal vaccines in development are swallowed as pills.