The Covid Vaccine We Need Now May Not Get Injected

On the outskirts of this centuries-old Indian city, a world away from its bustle and congested streets, Bharat Biotech’s modern labs are producing a Covid vaccine that instead of being injected, will take the form of a nasal spray.

As several studies have recently demonstrated, the vaccines available today offer strong, long-lasting immunity against severe Covid symptoms. But the protection they provide against contagion by the coronavirus is fleeting and can be weakened when new variants of the virus appear, a failure that has led to suggestions that regular booster doses would be needed.

In the long term, it is possible that nasal vaccines are the best way to prevent infections, because they offer protection exactly where it is needed to ward off the virus: in the mucous membranes of the airways, always the first point of arrival for the coronavirus.

Bharat Biotech is one of the world’s largest vaccine manufacturers. Its best-known product, Covaxin, has been authorized for the prevention of Covid in India and many other countries. But it’s their experimental nasal vaccine that could turn out to be truly revolutionary.

In an epidemic situation, immunizing entire populations with a nasal or oral vaccine would be faster than with an injected vaccine, which requires skill and time to administer. For many people, including children, a nasal shot may be more tolerable than painful injections. And shortages of needles, syringes and other materials would be avoided.

Intranasal vaccines “can be easily administered in mass immunization campaigns, reducing transmission,” said Krishna Ella, president and managing director of Bharat Biotech.

There are at least a dozen other nasal vaccines in development around the world, some of which are already in phase three clinical trials. But it is Bharat Biotech that may be the first to be made available. In January, the company obtained authorization to start a phase three trial of the nasal spray in India as a booster for people who have already received two injections of a Covid vaccine.

The omicron variant made it very clear that even three doses of a vaccine, while providing strong protection against severe symptoms, may not prevent contagion. This is because injected vaccines produce antibodies in the blood, comparatively few of which reach the nose, which is the gateway for the virus.

Ideally, so-called mucosal vaccines would coat the mucous membranes of the nose, mouth and throat with long-lasting antibodies and would be much more effective in preventing infection and spread of the virus. It’s the difference between placing guards at the gates to stop intruders and trying to drive out the intruders after they’ve already invaded the castle.

For immunologist Jennifer Gommerman of the University of Toronto, nasal shots “are the only way to really stop person-to-person transmission.” “We cannot live forever protecting vulnerable people and giving them booster shots to keep their antibodies at artificially high levels.”

Nasal vaccines have already been proven to protect mice, ferrets, hamsters and monkeys against the coronavirus. A new study reported last week brought strong evidence of its power as reinforcement.

An intranasal booster vaccine induced memory immune cells and antibodies in the nose and throat and reinforced the protection given by the initial vaccine, the researchers reported. The study has not yet been published in a scientific journal.

“Our proposal is not to use the nasal vaccine for primary vaccination, but as a booster, because with it it is possible to take advantage of and intensify the existing immunity that has already been created”, said Akiko Iwasaki, an immunologist at Yale University who led the study.

When she and her colleagues used a mix of proteins from the novel coronavirus and also from the virus related to Srag (severe acute respiratory syndrome), their experimental nasal vaccine appears to have been able to ward off a wide range of coronavirus variants.

“There is some flexibility, and there may be more resilience against the virus,” said Gommerman, who was not involved in the work. “And since we don’t know what the virus is going to do next, that’s highly attractive.”

Current Covid vaccines are injected into muscle and perform excellently at training immune cells to fight the virus once it has entered the body. They produce antibodies called IgG (from type G immunoglobulin) that circulate in the blood and can be summoned when needed.

But few of these antibodies reach the nose and throat, and even those that do lose strength in a short time.

Nasal vaccines produce a special set of antibodies called IgA (immunoglobulin type A) that thrive on mucosal surfaces such as the nose and throat. And those antibodies can take longer to weaken.

A vaccine delivered with a nebulizer could coat the entire airway, including the lungs, with IgA antibodies. “It’s not just the tip of the nose that is protected,” Iwasaki said.

“Location is really important, and mucosal immunity is really important for protection against infection,” said Michal Tal, a Stanford University immunologist who participated in the work.

People who acquire immunity because of an infection with the virus, rather than having received an injected vaccine, tend to have strong mucosal immunity, at least for some time. This, according to Tal, may help explain why they seem to have resisted the delta variant better than vaccinated people.

But she warned that trying to get infected for mucosal immunity is dangerous. “The right way for people to get this kind of mucosal protection is really to be with a nasal vaccine,” she said.

Still according to the immunologist, injectable vaccines are the correct approach to generate the systemic immunity necessary to prevent deaths and severe symptoms, the urgent objective at the beginning of the pandemic. And the Trump administration has promoted several candidates through its Warp Speed ​​operation.

“It was a good first step, but we needed to have intranasal vaccines ready to use as a booster soon after that,” she added. “I really wish we had a Warp Speed ​​2.0 operation for nasal vaccines.”

Translation by Clara Allain.