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Nasal vaccines may stop Covid infections. Will we get them soon?

Research on nasal vaccines is mostly in its early phases in the U.S., though many scientists believe this twist on vaccination could prove to be an effective way to block infections.
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In the early days of the pandemic, the federal government launched Operation Warp Speed, the public-private initiative aimed in part at speeding up the development of vaccines.

It proved to be a success, bringing the first Covid vaccines to the market in about 9 months, an unheard-of time frame for a process that normally takes years or even decades. 

But that same kind of effort has not been given to developing the next generation of vaccines, which experts believe will provide even greater protection.

Nasal vaccines, in particular, may hold a lot of promise; many scientists consider such an approach to have the potential to prevent infections entirely.

That’s because nasal vaccines deliver a boost of immunity right where the virus enters the body.

These vaccines “concentrate the immune protection in the upper airway,” Dr. Anthony Fauci, the White House’s chief medical adviser, told NBC News in an interview. In doing so, the “antibodies that are trying to protect you from having the virus enter your body, are right there on the front lines protecting you.”

The lack of initiative has been a disappointment for some scientists who say vaccines administered through the nose or upper respiratory tract may be better suited to preventing infections caused by the coronavirus compared to shots administered intramuscularly.

“There isn’t a lot of appetite to invest in these things anymore because Operation Warp Speed is over and a lot of people think this is all done and we don’t need better vaccines,” said Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai in New York City. He is supporting an effort at Mount Sinai to develop a nasal vaccine.

But as the pandemic continues, it’s clear that the existing vaccines do little to protect against infection, particularly from omicron and its family of immune-evading subvariants. The shots and boosters from Pfizer-BioNTech and Moderna continue to hold up against hospitalization and death, but blocking infection entirely could prevent even mild illnesses. It could also curb transmission of the virus and prevent other serious issues, such as long Covid.

“A traditional shot in the arm, you get what’s called systemic immunity, namely antibodies build up that are essentially distributed in different organs of the body,” Fauci said. That’s the reason, he said, those vaccines do very well against protecting against severe disease.

Nasal vaccines are also designed to induce antibody production, but in the mucosal tissue — the inner lining of the nose, throat and mouth, where the virus typically enters the body.

To effectively protect against infection, “you need mucosal immune responses,” said Michal Tal, an immunologist at Stanford University.

Nasal vaccines in the U.S.

A nasal vaccine still remains far off in the United States, though that isn’t for lack of trying: There are numerous nasal vaccines for Covid in development in the country, Fauci said, but the vast majority are still in the preclinical stage or early on in human clinical trials. The National Institute of Allergy and Infectious Diseases, which Fauci directs, is funding some early research on nasal vaccines.

Akiko Iwasaki, an immunologist at Yale University, is among the group of researchers working on a nasal vaccine.

Her team is looking at two approaches: a protein-based nasal spray and an mRNA vaccine delivered into the nose using nanoparticles.

In both, the nasal vaccine is intended to be used as a booster dose, building upon the existing immunity that was created through previous vaccinations, Iwasaki said. 

The strategy is called “prime and spike,” she said. “Prime is any sort of mRNA vaccine that has already been approved for Covid. And spike is the nasal booster.”

She and her colleagues have so far seen promising results in preclinical studies, posting data to a preprint server this year that found the nasal vaccine administered as a booster dose generated a strong immune response in the respiratory tracts of mice. 

Krammer, of Mount Sinai, is working on a nasal vaccine that’s currently in a phase 1 trial in the U.S. and a little bit further along in Mexico.

If the U.S. trial is successful, they hope to begin phase 2 sometime next year, he said.

This vaccine uses a modified version of a virus that usually infects birds to target the spike protein of the coronavirus, he said. The vaccine was found to generate an immune response in mice.

Research is further along in other countries: In India and China, for example, phase 3 trials are underway.

A long way to go

Fauci cautioned that nasals vaccines in the U.S. are still "a couple of years" away. Unlike Operation Warp Speed, which benefited from generous funding from the government, Congress has provided little for additional vaccine research, he said.

While the early findings are promising, there's no guarantee that any of the vaccines will end up being successful, he said.

Only one nasal vaccine is approved for use in the U.S.: FluMist, an influenza vaccine. But FluMist, though an appealing option for children who are afraid of needles, is less effective than the traditional shots.

If the research does pan out, Fauci said he's hopeful that a nasal vaccine would be available in "a couple of years." There also is no guarantee any of the vaccines will be successful, he added.

But “any product that looks promising, I can assure you, the FDA would be very anxious to look at it,” he said.

According to Iwasaki, the Yale immunologist, even a successful nasal vaccine is unlikely to be the final inoculation a person needs against Covid.

The nasal vaccine “is likely going to have to be repeated just as any other boosters, not just because of waning immunity, but potentially because of variants of concern that might arise" that can dodge immunity, she said.

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