The development of highly effective COVID vaccines in less than a year is an extraordinary triumph of science. But several coronavirus variants have emerged that could at least partly evade the immune response induced by the vaccines. These variants should serve as a warning against complacency—and encourage us to explore a different type of vaccination, delivered as a spray in the nose. Intranasal vaccines could provide an additional degree of protection, and help reduce the spread of the virus.

The currently authorized vaccines are injected into the muscle of the upper arm. Through a variety of mechanisms, they simulate a coronavirus infection. To fight off this perceived attack, the immune system mobilizes antibodies and T cells. As a result, in the event of an actual coronavirus infection, the immune system is prepared with a strong defense.

This approach can be enormously effective in reducing the risk of illness. Among nearly 600,000 people in Israel who have been fully immunized with an injected coronavirus vaccine, there has been a 94 percent decline in symptomatic cases of COVID, according to research by the country’s largest health care provider. However, worrisome new coronavirus variants have the potential to substantially erode that impressive efficacy.

For example, mutations in one variant, called B.1.351, have made at least three of the current vaccines less effective, based on data from clinical trials. A separate variant, called B.1.1.7, has been linked to more than 40 percent greater transmissibility, nearly 30 percent higher mortality, and a longer period of infectiousness. These characteristics could explain peaks in COVID cases, hospitalizations, and deaths that have occurred in the U.K., Israel, Ireland, and Portugal.

Although injected vaccines do reduce symptomatic COVID cases, and prevent a lot of severe illness, they may still allow for asymptomatic infection. A person might feel fine, but actually harbor the virus and be able to pass it on to others. The reason is that the coronavirus can temporarily take up residence in the mucosa—the moist, mucus-secreting surfaces of the nose and throat that serve as our first line of defense against inhaled viruses. Research with laboratory animals suggests that a coronavirus infection can linger in the nose even after it has been vanquished in the lungs. That means it might be possible to spread the coronavirus after vaccination.

Enter the intranasal vaccine, which abandons the needle and syringe for a spray container that looks more like a nasal decongestant. With a quick spritz up the nose, intranasal vaccines are designed to bolster immune defenses in the mucosa, triggering production of an antibody known as immunoglobulin A, which can block infection. This overwhelming response, called sterilizing immunity, reduces the chance that people will pass on the virus.

We have seen this movie before. The first successful polio vaccine, developed by Jonas Salk and licensed for use in 1955, was injected. Like current coronavirus vaccines, it substantially reduced the risk of illness, but did not always prevent infection.

Poliovirus is spread through food or water contaminated with human excrement. The virus enters the body through the mucosa of the gut, then infects the nervous system, where it can cause paralysis. In 1960, Albert Sabin introduced a new polio vaccine, which contained a weakened form of poliovirus, rather than the completely inactivated virus in the Salk vaccine. But the most striking difference was that Sabin’s vaccine was swallowed, in the form of a sugar cube or a liquid. In this way, it could come into direct contact with the gut mucosa. This made it more effective than the Salk vaccine in blocking poliovirus infection.

So there is precedent for designing a vaccine that strengthens our immune defenses on the front lines. This is true for respiratory viruses as well as for those that infect the gut. We have flu vaccines, for instance, because before the SARS outbreak in 2003--also caused by a novel coronavirus--the respiratory virus most feared for its potential to spark a pandemic was influenza. The 1918 flu pandemic claimed 50 million lives worldwide. Today although injected influenza vaccines are more familiar, intranasal versions exist and have a long history. First used in the 1960s in the former Soviet Union, intranasal influenza vaccines have proved to be effective. They are currently being manufactured in the U.S. and India.

Yet among the hundreds of coronavirus vaccine candidates that are in various stages of development around the world, only a small fraction are intranasal. So far, they have not received large-scale government support. But the early research and development efforts focused on the mucosal route do appear to be promising.

In a study using laboratory animals, an experimental intranasal vaccine created by scientists at the Washington University School of Medicine induced a powerful immune response in both the mucosa and the rest of the body, almost entirely preventing infection. Another animal study further demonstrated the important role of the mucosa in preventing infection. The researchers developed an intranasal spray that made it difficult for the coronavirus to attach to human cells. Used daily, it was able to entirely block transmission of the virus. At least four intranasal vaccines have progressed to the first phase of clinical testing with people, in China, India, the U.K., and the U.S.

Intranasal vaccines have some practical advantages, too. Unlike an injection, a nasal spray is painless. The absence of a needle might allay the concerns of those who are now hesitant about vaccination. An intranasal vaccine can also be self-administered at home, with minimal instruction. And some of the intranasal vaccines now being tested require no refrigeration, making them easy to transport and store, especially in l0w-resource countries.

All of these factors will become even more important if periodic booster vaccinations are needed to protect us against emerging coronavirus variants. Simply mailing someone a nasal spray is far more convenient than arranging for an in-person injection.

We will bring the COVID pandemic under control when we successfully reduce the spread of the coronavirus to extremely low levels. But the presence of vaccinated asymptomatic carriers could make this very difficult to do. For this reason, it seems imperative that new investments in vaccine research and development include substantial funding for intranasal vaccines. With their potential to block coronavirus infection—and with many fewer distribution and administration hassles—intranasal vaccines appear to be a smart bet. It is time to make them a priority, and accelerate their development.