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May 31, 2022, 8:45 a.m. EDT

Nasal COVID vaccines are being tested in 7 clinical trials — how would they work?

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By Mayuresh Abhyankar

Imagine inhaling just a few drops of liquid or mist to get protected from COVID-19. That is the idea behind nasal COVID-19 vaccines, and they have been getting a lot of attention recently as a spray or liquid. These nasal vaccines would be based on the same technology as normal vaccines given by injection. But as Mayuresh Abhyankar, a University of Virginia researcher who studies infectious diseases and works on nasal vaccines, explains, vaccinating someone right where the coronavirus is likely to start its attack comes with many immunological benefits.

1. What are nasal vaccines?

Nasal vaccines are administered, as the name suggests, through the nose. More accurately called intranasal vaccines, these vaccines are liquids that can be given as a spray or through a dropper or syringe.

The  most common nasal vaccine is FluMist , a nasal spray that uses inactivated flu virus to protect against influenza. An intranasal vaccine could be a weakened live virus similar to FluMist, a nucleic acid vaccine  like mRNA coronavirus vaccines  or a protein vaccine like hepatitis B vaccines or  the CorbeVax coronavirus vaccine .

Intranasal vaccines are best suited to protect against pathogens that enter through the nose, like the flu or the coronavirus. By mimicking the first step of natural exposure to an airborne pathogen, these vaccines help train a person’s immune system at the potential place of infection.

Scientists have shown that the first immune response in the respiratory tract after a person is exposed to an airborne virus can  influence how sick a person gets . So in theory, intranasal vaccines could  provide better protection  than vaccines given through a shot in the arm.

2. How does the coronavirus infect people?

SARS-CoV-2, the virus that causes COVID-19, usually enters the body through the nose and lands on the mucus membrane at the back of the nasal passage and in the throat. The virus then enters the cells it touches, replicates and spreads.

Just underneath these cells of the mucus membrane are many types of immune cells that form what is called the  mucosal immune system . Cells of the mucosal immune system are the first to identify invading coronavirus particles and start mounting a protective response.

In an unvaccinated individual, it takes about  two weeks for these immune cells to build up a protective response  after encountering the coronavirus. By that time, the virus can easily have infected other body parts, like the lungs, which can  lead to severe disease .

Nasal vaccines follow a lot of the same steps. When you inhale a nasal vaccine, the particles land on the mucus membrane in your nasal cavity or the back of your throat, enter the cells in those places and trigger an immune response. This process teaches the body about the coronavirus and allows it to deal with any future real infections.

3. How are nasal and intramuscular vaccines different?

When you get a COVID-19 shot in your arm, the vaccine triggers a strong immune response in the cells near where you got the shot. It also causes your immune system to produce some coronavirus-specific antibodies and other immune cells in other locations throughout your body.

When the coronavirus begins infecting cells in a person’s respiratory tract, the immune cells nearby will start mounting a defense. Your body will also  send anti-viral immune cells and antibodies  from other locations to the site of infection. But by the time enough coronavirus-specific immune cells gather around the infection site to stop the virus from replicating, the virus has likely already begun to spread throughout the body, making it difficult for the immune system to keep up.

Nasal vaccines mimic the virus in order to  prepare the immune system against a virus , just like any other vaccine. But importantly, they mimic the process of infection, too, and boost protective response within the  mucosal immune system of the nose and throat . In simple terms, intranasal vaccines are like knowing there is going to be a break-in and putting your guards in the right location before the trouble even starts.

The science bears this idea out. In a head-to-head comparison, AstraZeneca’s /zigman2/quotes/200304487/composite AZN +0.42% /zigman2/quotes/203048482/delayed UK:AZN +0.16% COVID-19 vaccine provided  greater protection in hamsters that were vaccinated intranasally  compared to those vaccinated intramuscularly.

Nasal vaccination could also be used in concert with intramuscular immunization. In a recent study, my colleagues and I gave some mice both a nasal and intramuscular vaccine and exposed them to a lethal dose of SARS-CoV-2— 100% of these mixed-vaccinated mice survived , compared to only 10% of the unvaccinated mice.

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