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Reviews | Nasal Covid vaccine could prevent infections


The Covid-19 vaccines authorized for use today have been developed at unprecedented speed and have exceeded expectations for their efficacy. The billions of people who are protected from it have avoided severe symptoms, hospitalizations and deaths. These vaccines are a scientific success beyond measure.

And yet, they could be even better.

The enemy has evolved and the world needs next-generation vaccines to respond to it. This includes vaccines that completely prevent coronavirus infections.

When the first mRNA vaccines were first licensed in December 2020, the world was facing a different kind of pandemic. The dominant circulating strain had a relatively low ability to spread between people. At that time, mRNA vaccines not only offered strong protection against serious illness and death, but they also offered high protection against infection and the spread of the virus.

But SARS-CoV-2 continued to mutate, and in the process gave rise to variants that were more contagious and highly capable of circumventing protective antibodies, causing widespread infections, despite ever-increasing levels of vaccine immunity. and previous infections. Fortunately, after the booster, mRNA vaccines are still very effective in preventing hospitalizations and deaths, including against the highly contagious variant of Omicron.

So, one might ask, if we can eliminate much of the risk of serious illness and death through a combination of vaccines and existing treatments, why should we worry about infections?

Even mild infections can turn into prolonged Covid, with people suffering from long-lasting debilitating symptoms. The data also suggests that groups like older people who have been vaccinated but have not received their boosters may continue to be at higher risk of experiencing the worst outcomes from Covid-19. Regular infections can significantly disrupt people’s lives, affecting their ability to work and keep their children in school. There is also no guarantee that people infected with Omicron will remain protected against infection by future variants.

One change that could make vaccines more effective is if they can stop the virus in its tracks, just as it enters the body. This could completely reduce infections, as well as the spread of the virus.

Currently available Covid-19 vaccines are injected into people’s arm muscles and are very capable of fighting the virus once people are infected. But they don’t do as well at preventing people from getting infected to begin with. To do this, you ideally want to prevent a virus from spreading directly to the site where people are infected: the nasal cavity.

Groups of scientists, myself included, are working on nasal Covid vaccines for this very reason. Ideally, a nasal vaccine could penetrate the layer of mucus inside the nose and help the body make antibodies that capture the virus before it even has a chance to attach to people’s cells. This type of immunity is known as sterilizing immunity.

By catching viruses directly at the site of infection, antibodies induced by nasal vaccines can give the body a head start in fighting off the virus before it causes symptoms. Not only could nasal vaccines be in a better position to prevent infections, but they can also develop the same type of immune system protection as other vaccines, and even stronger because this immune memory is at the front door of the virus. . These vaccines can establish highly protective memory B cells, which make antibodies faster and better against future infections, and memory T cells, which help kill infected cells and support antibody production.

These types of vaccines have traditionally been considered more difficult to manufacture. The mucus layer is a formidable barrier. Nor does the body generate a robust immune response by simply spraying a conventional vaccine into the nose. The approved nasal flu vaccine, called FluMist, uses weakened viruses to enter cells in the nose and stimulate an immune system response. But this approach is not safe for use in immunocompromised people.

The good news is that scientists like me think we’ve found a way around this problem for SARS-CoV-2. We have shown in animal studies that we can spray the so-called spike proteins of the virus into the nose of a previously vaccinated host and significantly reduce nose and lung infection as well as provide protection against disease and dead. Combining this approach with ongoing efforts to develop a single vaccine for a wider range of coronaviruses could also offer people protection against future variants.

A big question is how long immunity from a nasal vaccine would last. So far, in animal studies, antibodies and memory immune cells persist in the nose for months. If that immunity wanes over time, as with other vaccines, using the nasal spray as a booster — potentially over-the-counter — every four to six months may make the most sense for this pandemic. This presents similar challenges to other boosters, where uptake could be much higher, especially for high-risk groups. Encouraging people to get their reminders is essential. But the barrier for a nasal spray booster may be lower for many people than for a needle injection.

The world desperately needs a vaccine strategy that puts immunological guards outside the gates to prevent viral invaders from infecting us. There are several other nasal vaccine approaches in various phases of clinical trials. And any successes we will have in developing a nasal vaccine against Covid-19 will not be limited to this one virus. Nasal spray vaccination strategies can also be applied to other respiratory pathogens.

Although some hurdles remain, the potential immunological and public health benefits of nasal spray vaccines merit consideration now and for years to come.

Akiko Iwasaki (@VirusImmunity) is a professor of immunobiology at the Yale School of Medicine and a research scientist at the Howard Hughes Medical Institute. She is also co-founder of Xanadu Bio, a start-up that hopes to produce and test a nasal spray vaccine.

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