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New nasal spray vaccines might reduce COVID infections, but the money is still missing

New nasal spray vaccines might reduce COVID infections and cut off transmission. But data supporting the approach, and funding for clinical trials, is scant.

Dozens of academic labs and biotech firms, including Moderna, are working on nasal vaccines.RUTH FREMSON/NYT/file

The vision is enticing: replacing the pain of a vaccine shot with a nasal spray that is powerful enough to prevent even mild infections and short-circuit the global spread of COVID-19.

Even as Americans roll up their sleeves for updated fall boosters, new variants with the potential to evade immunity are spreading in parts of Europe and Asia, renewing calls among some experts for next-generation vaccines that can truly conquer the virus.

“We’re really at a crossroads now with COVID,” said Martin Moore, founder and chief scientific officer of Meissa Vaccines. “If we don’t block transmission, we’ll continue to have new variants, we’ll continue to have outbreaks, and we’ll have a heavy burden of endemic disease.”


While current shots are effective at preventing severe disease and death, they haven’t protected people from catching the virus. Some scientists say nasal vaccines will do a better job, because they stimulate a special class of antibodies in our noses that would stop the virus at the door, blocking infection.

Dozens of academic labs and biotech firms, including Moderna, are working on nasal vaccines. A few countries, including India, recently approved them. Prominent researchers are calling for a coordinated effort to accelerate their development in the United States. And the White House is asking Congress for $8 billion to develop intranasal vaccines and other COVID shots that could protect us from future variants of the coronavirus.

Yet despite the bullish excitement for the needleless approach, the future of the vaccines is clouded by a flurry of questions; most crucially, how safe and effective they are in humans.

“None of these vaccines have been tested to prove that they can prevent transmission or infection,” said Karin Bok, deputy director of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases. “It’s not clear how we’re going to get that done, and at the very least, it is going to take a couple of years to get there.”


Several researchers have called for a sequel to Operation Warp Speed, the government’s $12 billion program that accelerated the testing of the initial COVID vaccines and bankrolled their production. A similar program, they say, could help get intranasal vaccines to the masses.

This August 2022 photo provided by Pfizer shows vials of the company's updated COVID-19 vaccine during production in Kalamazoo, Mich. Associated Press

Plans for that sequel are in the works according to Dr. Ashish Jha, the White House COVID-19 response coordinator. In September at Globe Summit, The Boston Globe’s annual conference, Jha said the Biden administration is proposing an effort called “Project COVID Shield” to speed next-generation vaccines and therapies.

The administration requested $8 billion to support the project as part of a $47 billion budget proposal largely focused on the COVID pandemic and support for Ukraine. But debate on the vaccine funds was punted to avoid a government shutdown. White House press secretary Karine Jean-Pierre said Tuesday that the administration wouldn’t give up on trying to secure that funding.

The outlook for private funding is no more promising. Most pharmaceutical companies have eschewed the needle-free vaccines, partly because of a lack of safety data, and venture capital firms are not rushing to invest in the approach either, leaving many startups and academic labs wondering how to pay for clinical studies.

Although there are close to 100 intranasal COVID vaccine programs worldwide, the vast majority of them are in preclinical stages of development. India, Iran, and Russia approved intranasal vaccines for COVID without disclosing any data on how protective the products are.


One of those vaccines, from the Indian vaccine company Bharat Biotech, was licensed from Washington University in St. Louis early in the pandemic, where it was invented in the labs of Dr. David Curiel and Dr. Michael Diamond. On Wednesday, the small Pennsylvanian biotech company Ocugen announced that it had a license from the university to develop the vaccine as a booster in the United States, Europe, and Japan.

That vaccine uses an engineered common cold virus, similar to the COVID shots made by AstraZeneca and Johnson & Johnson, to deliver genetic instructions for a piece of the coronavirus into the nose. The goal is to mimic a natural infection and recruit specialized immune cells and antibodies to prevent the virus from gaining a foothold.

The Bharat vaccine was approved for people who hadn’t received COVID shots yet in India, but companies expect that the biggest market for intranasal vaccines in the United States will be as boosters.

Four American startups — CastleVax, Codagenix, CyanVac, and Meissa Vaccines — are already conducting safety studies of their intranasal boosters in people. Those vaccines are each based on different respiratory viruses engineered to trigger immunity against COVID without causing disease.

Enrolling volunteers for the studies has taken longer than expected. Most firms haven’t disclosed timelines for when larger and more advanced clinical trials will happen but caution that they could take at least another two years.


Pfizer has no plans to reformulate its shot as a nasal spray.Jeenah Moon/Getty Images

The firms with the most resources to make intranasal vaccines a reality have shown little interest in the approach. Plans to develop reformulated intranasal versions of the AstraZeneca and Johnson & Johnson vaccines, now given as shots, have seemingly stalled. And Pfizer has no plans to reformulate its shot as a nasal spray.

Moderna’s commitment to the idea is unclear. The company is working with scientists at the National Institutes of Health to test intranasal boosters of its mRNA vaccine in monkeys, according to Dr. Robert Seder, chief medical officer of NIH’s Vaccine Research Center. But Moderna has not disclosed the program and did not respond to requests for more information on the vaccine.

The largest active test of an intranasal vaccine is a 20,000-person study of Codagenix’s nasal drip immunization. The trial, sponsored by the World Health Organization, is focused on countries with low vaccination rates.

If the vaccine is effective, Codagenix chief executive J. Robert Coleman said, it could be widely deployed in Africa, Latin America, and Southeast Asia next year. But when, or if, the vaccine becomes available in the United States partly hinges on what data the Food and Drug Administration will require from companies hoping to sell intranasal vaccines as boosters, Coleman added.

So far, the FDA has approved COVID boosters based on their ability to raise antibody levels in the blood. But the purported benefits of intranasal vaccines are thought to derive from the mucosal immune responses in our airways, which are notoriously tricky to measure.


Matt Stober, chief executive of CastleVax, said that if nasal spray vaccines trigger blood antibody levels equivalent to the mRNA boosters, approval could come quickly. If that doesn’t happen, companies may need to run large clinical trials to determine exactly how protective the vaccine is.

Regulators may deem larger studies necessary in any case since many intranasal vaccines are based on technologies with little to no safety record in humans.

An intranasal flu vaccine tested in the 1990s was linked to facial paralysis, an event that still looms large in the minds of many vaccine scientists. Because the sinuses are close to the brain, there’s a fear that virus particles could weasel their way in there and cause damage.

“The big hurdle to overcome will be safety,” Bok said. “Administering a vaccine so close to the brain is really not a joke.”

Ryan Cross can be reached at Follow him on Twitter @RLCscienceboss.