Your Next COVID Vaccination Could Be a Nasal Spray: Here's Why

Nasal vaccines build immunity in the nose, where the COVID virus enters the body.

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Researchers are working on a new approach to COVID-19 vaccination that will be delivered in the form of a nasal spray, which may mean the future of vaccines could be as simple as inhaling a few drops of liquid instead of a shot in the arm.

While traditional injectable vaccines have been highly successful and effective at saving millions of lives around the globe and preventing severe disease, hospitalization, and death, they have not blocked the virus from spreading person to person.

The spray, by contrast, is being designed to stop the virus at what is widely acknowledged to be its most common point of entry: the nose.

"The whole point of a nasal vaccine or a vaccine that occurs at the site of infection (like the nose) is that there are specialized immune cells that can live and reside in those tissues and act faster to prevent that invading pathogen from infecting you," Benjamin Goldman-Israelow, MD, PhD, assistant professor of internal medicine and infectious diseases at Yale School of Medicine, told Health. "If you have fewer hosts that are transmitting the virus, it gives it less opportunity to evolve and create new variants."

Not only would nasal sprays better prevent transmission, but they could also slow down progression of the virus, and halt the quick cycle of emerging variants, said Dr. Goldman-Israelow.

With numerous researchers at work on this initiative, here's everything you need to know about the future of COVID nasal vaccine sprays.

How Do Nasal Sprays Work?

Nasal sprays are made up of small liquid or solid particles that are formulated to be distributed in the nasal cavity, delivering drugs and vaccines for respiratory diseases, Ramasamy Paulmurugan, PhD, professor of radiology at Stanford University, told Health. Nasal sprays are also designed to carry antigens, which are proteins of infectious agents—such as viruses—that induce an immune response in the body.

When these types of vaccines are introduced into the nasal cavity, the antigen attracts immune cells and induces some of these cells to produce antibodies, which are sometimes referred to as the protective soldiers of the immune system. The nasal vaccine also activates other immune cells that will remember the invader so they can easily spot and neutralize the threat, according to a Stanford press release.

The nasal vaccines are an important step forward because they will deliver immunity specifically to the nasal mucosa and sinus cavities, which can then—because the nose is the portal entry for the virus—fight respiratory viruses like COVID and flu, Linda Yancey, MD, infectious disease specialist, Memorial Hermann Health System in Houston, told Health.

"If we can provide robust immunity right as we are first being exposed to the virus, we can theoretically fight it off faster and better," Dr. Yancey said.

Benefits and Drawbacks of Nasal Sprays

In addition to the primary advantage already mentioned—stopping the virus at the entry point in one's nose—the nasal spray vaccines have other benefits.

For instance, it's not unusual for individuals to have phobias of needles or simply want to avoid them. Nasal sprays allow such patients to circumvent such concerns. As a result, offering a nasal spray vaccine rather than an intramuscular vaccine may increase overall utilization of COVID-19 vaccination, Dr. Yancey said.

Nasal vaccines can also be easier to administer and handle as health care providers don't need to deal with sharp objects or potential exposure to blood products, Dr. Yancey added.

"They are simpler and more efficient for everyone involved," Dr. Yancey said. "Nasal vaccines also deliver immunity right where it is needed most, to the portal of entry for the virus in our nasal passages."

In terms of limitations, storage conditions could be a concern with nasal vaccines, Dr. Goldman-Israelow said. But that's a constraint with all vaccines including the intramuscular injections currently in use. Additionally, because nasal spray vaccines for COVID are still in the early stages of development, researchers have not yet determined whether they provide as robust or as long-lasting immunity as injectable vaccines.

"There are many different types of nasal vaccines which probably work differently, but we have no evidence right now that a nasal vaccine would necessarily lead to less kind of prolonged immunity or less durable protection than intramuscular vaccines," Dr. Goldman-Israelow said.

There are other potential limitations as well, Tarik Massoud, MD, PhD, professor of radiology at Stanford University, told Health.

"For example, we do not know yet whether it would be sufficient to expose the upper or lower parts of the respiratory tract to vaccines," Dr. Massoud explained. "As for all therapeutics, we will need to determine the safety, efficacy, and acceptability of our new nasal vaccine."

When Will Nasal Vaccines Become Available?

There are several COVID nasal spray vaccines in production at the moment and each is in a different phase of the testing and review process. Most of them are in pre-clinical or phase one trials in the United States. Other nasal spray vaccines, mainly international trials, are in phase two or three trials.

According to the Centers for Disease Control and Prevention (CDC), clinical development is a three-phase process. In phase one, small groups of people get the trial vaccine. In phase two, the clinical study expands and the vaccine is given to people who have characteristics like age and physical health similar to those for whom the vaccine is intended. In the last phase, the vaccine is tested for efficacy and safety and is given to thousands of people.

For the nasal vaccines to advance and become available to the public, extensive testing is needed, Dr. Yancey said. The testing will include various aspects of nasal delivery, and human testing must take place—which is already occurring in some trials. Once the data has been examined and safety protocols have been validated, the nasal spray vaccines will be able to move on to phase two trials.

"This is going to take some time, as all clinical trials do. That being said, we are still in a pandemic and the FDA has prioritized review of these vaccines," Dr. Yancey said. "Given that the world is still seeing high levels of COVID transmission, any vaccine that shows efficacy will likely have a robust market for it."

Funding will be another hurdle to clear in order to bring the nasal sprays to the public. Significant funding from private and public sources—including support from the government—is critical to continue studying all aspects of nasal spray vaccines, said Dr. Goldman-Israelow.

"At the onset of the pandemic, we saw a lot of investment by governments and others which were pumping huge amounts of dollars and resources into developing the vaccines that came out," Dr. Goldman-Israelow said.

"We need this next phase of the pandemic to be supported similarly, because how we exit this pandemic and move into a phase where we can return to normal, really depends on how quickly we can develop the next generation of vaccines, which include intranasal vaccines," Dr. Goldman-Israelow added.

Based on all of these factors—the clinical trials, the funding requirements—experts estimate it could take anywhere between two to five years before a nasal vaccine becomes available for public use.

"If everything goes perfectly and they [researchers and drug companies] get the numbers they need to present to the FDA, we could see these as soon as 2023," Dr. Yancey said. "If they run into issues with production or trial recruitment or unexpected findings pop up, that timeline could extend to five years to never."

Not everyone however, is as confident about that two to five year timeline.

"Those trials may not find that the vaccines are effective or safe. Until we have those results, there's no way to predict availability," Andrew Handel, MD, pediatric infectious diseases expert at Stony Brook Children's Hospital, told Health.

Despite how long it might take for COVID nasal spray vaccines to become available, experts agree that this type of vaccine can indeed be useful and effective at preventing infection and controlling the pandemic.

"Everyone is looking for the silver bullet that will end this pandemic. As the months have turned to years this is becoming increasingly unlikely," Dr. Yancey said. "COVID would appear to be with us to stay. The more tools we have to fight this the better, and the safer we can keep people. These nasal vaccines are going to be an important tool in our tool kit."

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