Scientists Aim to Combat COVID With a
Shot in the Nose

Kerry Dooley Young

July 27, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Scientists seeking to stay ahead of an evolving SARS-Cov-2 virus are looking at new strategies, including developing intranasal vaccines, according to speakers at a conference Tuesday.

The Biden administration held a summit on the future of COVID-19 vaccines, inviting researchers to provide a public update on efforts to try to keep ahead of SARS-CoV-2.

Scientists and federal officials are looking to build on the successes seen in developing the original crop of COVID vaccines, which were authorized for use in the United States less than a year after the pandemic took hold.

But emerging variants are eroding these gains. For months now, officials at the Centers for Disease Control and Prevention (CDC) and US Food and Drug Administration (FDA) have been keeping an eye on how the level of effectiveness of COVID vaccines has waned during the rise of the Omicron strain. And there's continual concern about how SARS-CoV-2 might evolve over time.

"Our vaccines are terrific," said Ashish K. Jha, MD, MPH, the White House's COVID-19 response coordinator, at the summit. "[But] we have to do better."

Among the approaches being considered are vaccines that would be applied intranasally, with the idea that this might be able to boost the immune response to SARS-CoV-2.

At the summit, Akiko Iwasaki, PhD, of Yale University, said the intranasal approach might be helpful in preventing transmission as well as reducing the burden of illness for those who are infected with SARS-CoV-2.

"We're stopping the virus from spreading right at the border," Iwasaki said at the summit. "This is akin to putting a guard outside of the house in order to patrol for invaders compared to putting the guards in the hallway of the building in the hope that they capture the invader."

Iwasaki is one of the founders of Xanadu Bio, a private company created last year to focus on ways to kill SARS-CoV-2 in the nasosinus before it spreads deeper into the respiratory tract. In a July 21 editorial in Science Immunology, Iwasaki and Eric J. Topol, MD, director of the Scripps Research Translational Institute, urged greater federal investment in this approach to fighting SARS-CoV-2. (Topol is editor-in-chief of Medscape.)

Titled "Operation Nasal Vaccine — Lightning speed to counter COVID-19," their editorial noted the "unprecedented success" seen in the rapid development of the first two mRNA shots. Iwasaki and Topol noted that these victories had been "fueled by the $10 billion governmental investment in Operation Warp Speed."

"During the first year of the pandemic, meaningful evolution of the virus was slow-paced, without any functional consequences, but since that time we have seen a succession of important variants of concern, with increasing transmissibility and immune evasion, culminating in the Omicron lineages,"  Iwasaki and Topol write.

Recent developments have "spotlighted the possibility of nasal vaccines, with their allure for achieving mucosal immunity, complementing, and likely bolstering the circulating immunity achieved via intramuscular shots," they add.

An Early Setback

Scientists at the National Institutes of Health and the Biomedical Advanced Research and Development Authority (BARDA) have for some time been looking to vet an array of next-generation vaccine concepts, including ones that trigger mucosal immunity, the Washington Post reported in April.

At the summit Tuesday, several participants, including Jha, stressed the role that public-private partnerships were key to the rapid development of the initial COVID vaccines. They said continued US government support will be needed to make advances in this field.

One of the presenters, Biao He, PhD, founder and president of CyanVac and Blue Lake Biotechnology, spoke of the federal support that his efforts have received over the years to develop intranasal vaccines. His Georgia-based firm already has an experimental intranasal vaccine candidate, CVXGA1-001, in phase 1 testing ( NCT04954287).

The CVXGA-001 builds on technology already used in a veterinary product, an intranasal vaccine long used to prevent kennel cough in dogs, he said at the summit.

The emerging field of experimental intranasal COVID vaccines already has had at least one setback.

The biotech firm Altimmune in June 2021 announced that it would discontinue development of its experimental intranasal AdCOVID vaccine following disappointing phase 1 results. The vaccine appeared to be well tolerated in the test, but the immunogenicity data demonstrated lower than expected results in healthy volunteers, especially in light of the responses seen to already cleared vaccines, Altimmune said in a release. 

In the statement, Scot Roberts, PhD, chief scientific officer at Altimmune, noted that the study participants lacked immunity from prior infection or vaccination. "We believe that prior immunity in humans may be important for a robust immune response to intranasal dosing with AdCOVID," he said.

At the summit, Marty Moore, PhD, co-founder and chief scientific officer for Redwood City, California-based Meissa Vaccines, noted the challenges that remain ahead for intranasal COVID vaccines, while also highlighting what he sees as the potential of this approach.

Meissa also has advanced an experimental intranasal COVID vaccine as far as phase 1 testing (NCT04798001).

"No one here today can tell you that mucosal COVID vaccines work. We're not there yet. We need clinical efficacy data to answer that question," Moore said.

But there's a potential for a "knockout blow to COVID, a transmission-blocking vaccine" from the intranasal approach, he said.

"The virus is mutating faster than our ability to manage vaccines and not enough people are getting boosters. These injectable vaccines do a great job of preventing severe disease, but they do little to prevent infection" from spreading, Moore said.

Kerry Dooley Young is a freelance journalist based in Miami Beach, Florida. She is the core topic leader on patient safety issues for the Association of Health Care Journalists. Follow her on Twitter at @kdooleyyoung.

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