Nasal vaccines under development around the world may make better boosters by stopping the coronavirus in the airways.

By Apoorva Mandavilli

On the outskirts of this centuries-old Indian city, a world away from its congested roads and cacophony, the gleaming modern laboratories of Bharat Biotech are churning out a Covid vaccine that would be sprayed into the nose rather than injected into the arm.

Currently available vaccines produce powerful, long-lasting immunity against severe illness, as several studies have recently shown. But their protection against infection from the coronavirus is transient, and can falter as new variants of the virus emerge — a failing that has prompted talk of regular booster shots.

Nasal vaccines may be the best way to prevent infections long term, because they provide protection exactly where it is needed to fend off the virus: the mucosal linings of the airways, where the coronavirus first lands.

Bharat Biotech is among the world’s leading vaccine manufacturers. Its best known product, Covaxin, is authorized to prevent Covid in India and many other countries. But its experimental nasal vaccine may prove to be the real game changer.

Immunizing entire populations with a nasal or oral vaccine would be faster in the middle of a surge than injections, which require skill and time to administer. A nasal vaccine is likely to be more palatable to many (including children) than painful shots, and would circumvent shortages of needles, syringes and other materials.

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

There are at least a dozen other nasal vaccines in development worldwide, some of them now in Phase 3 trials. But Bharat Biotech’s may be the first to become available. In January, the company won approval to begin a Phase 3 trial of the nasal spray in India as a booster for people who have already received two shots of a Covid vaccine.

A volunteer received a nasal form of the Sputnik V vaccine in Moscow last month.
A volunteer received a nasal form of the Sputnik V vaccine in Moscow last month.Credit…Mikhail Tereshchenko\TASS, via Getty Images

The Omicron variant made it all too clear that even three doses of a vaccine, while they provide powerful protection against severe illness, may not prevent infection. That’s because injected vaccines produce antibodies in the blood, comparatively few of which make it to the nose, the entryway for the virus.

So-called mucosal vaccines ideally would coat the mucosal surfaces of the nose, mouth and throat with long-lasting antibodies, and would be much better at preventing infection and spread of the virus. It is the difference between planting sentries at the gates to bar intruders and trying to oust them after they had already stormed the castle.

Nasal vaccines are “the only way to really circumvent person-to-person transmission,” said Jennifer Gommerman, an immunologist at the University of Toronto. “We can’t live forever sheltering vulnerable people and boosting them so that their antibody levels stay artificially high.”

Nasal vaccines have been shown to protect miceferretshamsters and monkeys against the coronavirus. A new study last week offered powerful evidence in support of their use as a booster.

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

“Our approach is to not use a nasal vaccine as a primary vaccination, but to boost with nasal vaccine, because then you can leverage the existing immunity that’s already 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 new coronavirus as well as the related SARS virus, their experimental nasal vaccine seemed capable of fending off a broad range of coronavirus variants.

“There’s some flexibility, and there might be more resilience against the virus,” said Dr. Gommerman, who was not involved in the work. “And because we don’t know what the virus will do next, that’s awfully appealing.”

The current Covid vaccines are injected into muscle, and excel at training immune cells to tackle the virus after it enters the body. They produce antibodies called IgG that circulate in the blood and can be marshaled when needed.

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