Nasal vaccines could help prevent COVID-19 from spreading — if scientists can get them right

When SARS-CoV-2, the virus that causes COVID-19, infiltrates the body, it usually enters through the nose or mouth, then takes root and begins to multiply.

But what if it could never gain a foothold in the upper respiratory tract? That’s the promise of nasal COVID-19 vaccines, which aim to prevent infection by blocking the virus at the point of entry.

No nasal COVID-19 vaccine is yet available in the US — and it’s not clear if or when it will be — but multiple research teams in the US, including the National Institute of Allergy and Infectious Diseases, and abroad are working to it . Russian scientists are testing a nasal form of their Sputnik V vaccine in adult volunteers and researchers in India have received approval for a Phase 3 trial.
[time-brightcove not-tgx=”true”]

Many researchers are excited about the prospect of nasal vaccines for COVID-19. “Yes with an exclamation point,” said Troy Randall, an immunologist at the University of Alabama at Birmingham, when asked if they’re worth investigating.

In countries like the US, where about 76% of people have had at least one dose of the COVID-19 vaccine, nasal vaccines would be used primarily as booster shots by default, and some research teams are studying them specifically in this capacity. But if they prove effective and are eventually authorized, they could also give young children and those afraid of needles more options.

There is a long way to go. While oral vaccines are fairly common, FluMist is the only nasal vaccine approved by the U.S. Food and Drug Administration to fight a respiratory pathogen, which is used to prevent the flu in people ages 2 to 49. FluMist had been in development for decades but was briefly taken off the market due to efficacy issues, which could foreshadow the challenges ahead for vaccine researchers working to create a nasal COVID-19 vaccine.

Still, researchers hope that nasal vaccines could one day do what even the highly effective mRNA vaccines made by Pfizer-BioNTech and Moderna don’t: slow transmission enough to end the pandemic.

Shot in the arm COVID-19 vaccines introduce the body to genetic material from the SARS-CoV-2 virus and teach the immune system what to do when faced with the real thing. These injections have proven to be very good at preventing serious illness and death, but less adept at blocking infections, especially against highly contagious Omicron.

Nasal vaccines could theoretically prevent many infections by conferring ‘local’ immunity where it’s needed most: the nose. If it worked, a spritz would coat the upper respiratory tract with defenses similar to those generated by the body after a brush with the actual virus, says Dr. James Crowe, director of the Vaccine Center at Vanderbilt University Medical Center.

“You get the best immunity against virus pathogens by mimicking, to the greatest extent possible, the actual infection without causing disease,” says Crowe. “Stopping a virus in its tracks right on your doorstep is very attractive.”

When done right, Crowe says, nasal vaccines can be very effective, but developing them is difficult. They usually use live but weakened forms of a virus, introducing a “Goldilocks” challenge, Crowe says. Weaken the virus too much and the vaccine won’t work; not enough, and it could overstimulate the immune system, leading to side effects. The balance has to be perfect.

The nose is also a very different area than the deltoid, where shots are usually given. It’s an almost direct line to the brain, which clearly requires a different set of precautions, Crowe says.

The upper respiratory tract is also built to encounter foreign substances and therefore may not respond as quickly to a vaccine, says Benjamin Goldman-Israelow, an instructor at the Yale School of Medicine. He co-authored a recent study, not yet peer-reviewed, that examined how mice responded to nasal versus injected COVID-19 vaccines. The study found that mice developed a stronger immune response when first injected and then boosted with a nasal vaccine, as opposed to getting just a nasal vaccine.

That may be because the upper respiratory tract is equipped with natural defenses against invading particles — after all, they are the body’s gateway to the outside world — and so don’t always react strongly when first introduced. “By giving that first priming through the [injected] mRNA vaccine, we’re raising the immune system so that by the time we give the intranasal boost, the immune system already recognizes this as foreign,” Goldman-Israelow says.

Another rodent study by Yale researchers, published in December, found that mice vaccinated with a nasal flu shot were less likely to get the flu than those given an injected vaccine — a finding that could also apply to other respiratory diseases, such as COVID-19 . Animal studies by other research teams have also shown promising signs that nasal vaccines can prevent infections, especially when given as boosters.

Of course, large clinical trials – some of which are underway in other countries – are needed to know how a product will work in humans. “We can’t draw any conclusions about whether a nasal COVID-19 vaccine will work or not work until we see the data,” said Dr. Hana Mohammed El Sahly, professor of virology and microbiology at Baylor College of Medicine.

There have already been setbacks. Last year, the biopharmaceutical company Altimmun stopped testing a nasal COVID-19 vaccine candidate due to disappointing research results.

Nasal vaccines are hard to get right. In the early 2000s, long before the COVID-19 pandemic, a nasal flu vaccine used in Switzerland was found to be associated with Bell’s palsy, a form of facial paralysis that is usually temporary. By the time the study was published, it was no longer in clinical use.

FluMist, the nasal flu vaccine used in the US and first approved in 2003, has encountered no such safety concerns, but was briefly taken off the market due to efficacy issues. The U.S. Centers for Disease Control and Prevention’s advisory committee on vaccines did not recommend its use in 2016, citing data that it had been only 3% effective during the previous flu season. A reformulated version of the vaccine returned to the market for the 2018-2019 season. As it stands, “it appears to be working, and the data supports its continued use,” El Sahly says.

Still, FluMist is not approved for people 50 and older or younger than 2 years of age. It is also not recommended for immunocompromised individuals and some people with lung conditions such as asthma. That’s because it contains a live but attenuated virus: an effective way to mount an immune response, but one that can lead to potentially serious side effects in people with underlying conditions.

“It’s a balancing act,” Randall says. “You want the vaccine to be effective, but you don’t want it to actually hurt or cause you” [too much] inflammation.”

Leaps in vaccine science have made it easier, if not easy, to strike that balance. For example, the Yale team working on nasal vaccines created a formula that contains no adjuvants (a material often added to vaccines to elicit a stronger immune system response) in hopes of reducing side effects. The pandemic also means that there is a lot of interest and money available for developing new vaccine candidates, which has not always been the case.

But creating a vaccine to fight viruses that often mutate, such as the flu and SARS-CoV-2, will always be a challenge. That’s true whether researchers are developing a nasal vaccine or an injection in the arm, Randall says.

“We can make sure that the order we chose is the one that actually goes into the vaccine,” he says. But there’s no telling if the order in the vaccine will be the one “Mother Nature throws at us.” Such mismatches explain why the flu shot is much more effective in some years than in others.

So far, mRNA-based COVID-19 vaccines have held up well against new variants and offer strong protection against serious illness and death. However, Omicron was the best yet at evasion of vaccine-derived immunity, crushing a record number of cases and straining the health care system. This underlines the need for a tool that can prevent infections as well as serious diseases.

“Really, the goal is to reduce or even eliminate transmission,” said Tianyang Mao, a graduate student at Yale School of Medicine and co-author of the study on booster nasal vaccines for COVID-19.

Two years after the COVID-19 pandemic, the need is clear. But Yale’s Goldman-Israelow says his team is motivated to create a nasal vaccine not just for this pandemic, but the next. When the technology is ready for use, our country’s response could significantly amplify the next time a new threat emerges, just as decades of work on mRNA vaccines blossomed just in time to help with the COVID-19 pandemic. 19 pandemic.

If nasal vaccines had been available earlier to complement the COVID-19 vaccines we already have, he says they “could have helped reduce transmission and prevent the continuation of the pandemic we’ve seen.”

This post Nasal vaccines could help prevent COVID-19 from spreading — if scientists can get them right

was original published at “”