Without a nasal vaccine, the American advantage in the fight against Covid is at stake

India, Russia and Iran have authorized nasal vaccines. And while none of these have yet proven they can stop Covid transmission, officials say the US could find itself at a global disadvantage, particularly if a more deadly variant emerges. .

“Intranasal vaccines – variant-resistant vaccines – these are essential tools to have in the toolbox to protect Americans, not only for Covid but also for future pandemics and also for future biosecurity threats,” Ashish Jha , the administration’s Covid-19 response coordinator, told POLITICO.

Researchers working on nasal vaccines hope to be able to stop transmission of the virus by generating immunity against it in the nose and other parts of the upper respiratory system where the coronavirus enters the body. If confirmed in clinical trials, nasal vaccines would be superior to existing mRNA vaccines, which prevent severe disease but do not stop transmission.

Officials at the National Institute of Allergy and Infectious Diseases are aware of the danger of not developing such a nasal vaccine because it would protect people in the event of a more contagious and deadly coronavirus variant, said Karin Bok, deputy director by interim for pandemic preparedness. and emergency response at the agency’s vaccine research center.

The center mapped nasal and oral Covid vaccines in development in the United States and abroad. It is also testing nasal versions of the Moderna vaccine and two other types of injectable Covid-19 vaccines in monkeys, Bok said. But that is unlikely to lead to the approval of a nasal Covid vaccine in the United States soon, as funding for clinical trials and production is lacking.

Bok and Jha say the cost is high. If China were to develop a nasal vaccine capable of stopping Covid transmission, it could reverse the trajectory of the current pandemic, which is bringing the United States and much of China into lockdown.

Even though India, Iran, China and Russia have not proven that their non-injectable vaccines stop transmission, the potential is there, experts say.

“Countries with reduced transmission will be healthier, have stronger economies. And the United States needs to catch up,” said Marty Moore, founder and chief scientific officer of Meissa Vaccines, a small biotech company trying to develop a nasal vaccine in the United States.

transmission stop

Many scientists believe that the nose may hold the secret to stopping the transmission of the coronavirus, but there is no consensus yet on whether nasal vaccines may be more effective than injection vaccines, as evidence from clinical trials are needed to prove it.

A disagreement in Congress over how to pay for additional aid or if it is needed, along with major drugmakers’ disinterest in spending their own money on something that may not be very profitable, could mean that a foreign rival gets an advantage.

Writing in science immunology in July, Eric Topol, professor of molecular medicine at Scripps Research, and Akiko Iwasaki, professor of immunobiology at Yale, endorsed the potential of a nasal vaccine to stop transmission of the coronavirus. “Breaking the chain of transmission at the individual and population level will put us in a much better position to achieve containment of the virus,” they wrote, adding that “the prospect of achieving this with nasal vaccines is high.”

They called on the US government to support the development of Operation Warp Speed ​​2.0, modeled on the initiative that created the first Covid-19 vaccines in record time. The Biden administration is working on it, but funding issues and pandemic fatigue hampered his efforts.

Beyond efficacy, a nasal vaccine could appeal to people who fear needles and parents of young children who have mostly refused to have their children inoculated. By early October, only 9% of children aged 6 months to 5 years had received the vaccines, which were cleared by the FDA in June.

American technology in India

Apart from the government-funded research cited by Bok, two Washington University School of Medicine professors, David T. Curiel, a radiation oncologist, and Michael S. Diamond, a molecular microbiologist, invented the nasal vaccine licensed in India.

Curiel and Diamond told POLITICO they created it with the needs of the developing world in mind, given the lack of ultracold freezers needed to store mRNA vaccines. The two scientists licensed their vaccine to Indian drugmaker Bharat Biotech, which tested it in clinical trials partially funded by the Indian government. They’ve also tried to solicit interest from big US pharma on it “and there hasn’t been as much enthusiasm as we would have thought,” Diamond said.

Their vaccine, named iNCOVACC in India, is based on an adenovirus that delivers the coronavirus spike protein.

Bharat Biotech tested it both as a primary vaccination series and as a booster for those vaccinated with injectable Covid vaccines available in India. The company said clinical trials had “successful results” and side effects were comparable to other Covid-19 vaccines, but it has yet to publish the data in a peer-reviewed scientific journal.

India’s drug regulator has approved the two-dose vaccine, which comes in the form of nose drops, for adults who have never received a Covid-19 vaccine, Bharat Biotech said. The company has the right to sell it in India and most of the rest of Asia and Africa.

Elsewhere, the Coalition for Epidemic Preparedness Innovations, a global partnership funding the development of vaccines against epidemic threats, is developing a plan for nasal vaccine research projects.

“For example, we are investigating whether nasal vaccines could be an option for our all-in-one coronavirus vaccine program funding the development of vaccines against variants of Covid-19 and other coronaviruses,” said Melanie Saville, CEPI’s executive director of vaccines. Research and development.

CEPI nearly $5 million in seed funding to Dutch company Intravacc for a nasal vaccine candidate that could work against multiple coronaviruses.

There are now 95 nasal vaccines in development around the world, according to health data firm Airfinity. Six have reached final phase 3 clinical trials.

Mitigating expectations

But some scientists doubt a nasal vaccine could be a game-changer.

William Haseltine, a former Harvard Medical School professor and expert in HIV/AIDS and genomics, says enthusiasm about the potential of nasal vaccines to prevent infection should be tempered, given that natural nasal exposure to the virus does not prevent people from getting reinfected.

“Why the hell do you think that if you [spray] a vaccine in the nose… you can do better? he asked POLITICO.

Attempts to develop a nasal version of the AstraZeneca Covid-19 vaccine, the injectable version of which was widely used around the world at the start of the vaccination campaign, experienced a setback after only a minority of participants in an early-stage clinical trial showed some immune response in the respiratory mucosa.

Haseltine argued that scientists still don’t have a good understanding of nasal immunity and that government funding would be better directed to antiviral drugs that control Covid-19.

And Bok doesn’t think any of the existing non-injectable vaccines stop the transmission of Covid-19. “I would be very surprised if India or China allowed it with data proving that an intranasal vaccine is better than the ones we have,” she said.

Funding issues

Curiel and Diamond have approved their vaccine for potential use in the United States at Pennsylvania-based biotech Ocugen.

The company is seeking both regulatory and financial support from the US government to develop the vaccine as a booster, CEO Shankar Musunuri told POLITICO.

But without another Operation Warp Speed, there will be significant delays in the large-scale manufacturing, regulatory approval and distribution of a nasal vaccine, Topol and Iwasaki argued.

Iwasaki, who is working to develop a Covid-19 nasal booster vaccine, said she will likely need tens of millions of dollars to test it in clinical trials. “Just trying to do this as a small university lab is very different from a Warp Speed,” she told POLITICO.

This is unlikely to happen.

Congress passed last month a short-term measure to continue funding the government until December 16 without any additional money for Covid-19. The White House had requested $8 billion to fund the next generation of vaccines and therapeutics, including nasal vaccines.

“There’s no plan B: If Congress doesn’t fund this, it won’t happen,” Jha said. “America will fall even further behind China and other countries.”