How inhaled vaccines can change the picture of the pandemic

THE China approved on Monday the first inhaled vaccine for the Covid-19 and carved a new escape path in her time pandemic.

The new generation of inhaled vaccines is cited as hope for the new phase the pandemic is entering. Dozens of researchers and companies are preparing for the new vaccines, which will be administered either by spray or by drops, like common drugs. The question that now arises is the following: How will the new type of vaccines change the picture of the pandemic on the planet?

This week, an inhaled version of a vaccine for COVID-19, produced by the Chinese company CanSino Biologics in Tianjin, was approved for use as a booster dose in China. It is one of more than 100 vaccines that will be given through the mouth or nose. In theory, these vaccines could activate immune system cells in the thin mucous membranes that line the cavities in the nose and mouth, where SARS-CoV-2 enters the body, and quickly stop the virus in its tracks — before it spreads. . Vaccine developers hope that these “mucosal” vaccines will prevent even mild cases of the disease and prevent transmission to other people, achieving what is known as sterilizing immunity. Some mucosal vaccines are already approved for other diseases, including a sprayable flu vaccine. Animal experiments show that immunity to COVID-19 can be neutered.

Why might mucosal vaccines be better than conventional vaccines?

The COVID-19 vaccines currently in use do a good job of reducing the severity of the disease and preventing hospitalization, but they do not do as well at preventing mild disease or transmission.

One reason is that they are injected into the muscles. Intramuscular shots trigger an immune response that includes T-lymphocytes, which destroy infected cells, and B-cells, which produce antibodies that “neutralize” pathogens—binding to them to prevent them from entering healthy cells. These cells and antibodies circulate through the bloodstream. But they are not present in high enough levels in the nose and lungs to provide rapid protection. In the time it takes to travel there from the bloodstream, the virus spreads and the infected person becomes ill.

Mucosal vaccines can induce a whole-body immune response, but they can also activate immune cells in the mucosal tissue of the nose and respiratory tract. These localized cells “act as sentinels at the site of infection,” says Benjamin Goldman-Israelow, a physician-scientist at the Yale School of Medicine in New Haven, Connecticut. “They can act much faster.”

Localized mucosal immune cells, known as tissue-resident memory T and B cells, have slightly different functions than circulating T cells and B cells. For example, tissue-resident memory B cells produce antibodies called secretory immunoglobulin A (IgA), which are bound to the linings of the respiratory tract, where they may be able to quickly stop pathogens. However, it is unclear how well secretory IgA will protect against SARS-CoV-2.

Researchers are testing mucosal vaccines as first doses for unvaccinated people and as boosters for those who have already received COVID-19 vaccines. Some mucosal vaccines are identical to injectable vaccines, but are sprayed as a liquid or droplets into the nose. Others have a different composition or are prepared differently. For example, the mucosal vaccine developed by CanSino is the same as the injected one, but is aerosolized and inhaled orally with a nebulizer at one-fifth the dose of the injectable version. Some mucosal vaccines in development are swallowed as pills.

How good are mucosal vaccines against other diseases?

At least nine mucosal vaccines have been approved for use in humans against pathogens including polio, influenza and cholera viruses. Eight of these vaccines are taken orally and one, against influenza, is given intranasally.

The oral polio vaccine, which induces immunity in the gut, is highly successful and comes close to achieving sterilizing immunity. In rare cases, however, this live attenuated vaccine will mutate and cause disease. For other diseases, mucosal vaccines have not been as successful—sometimes because the vaccine does not generate a strong enough immune response, and sometimes because it causes side effects. The Swiss vaccine company Berna Biotech in Bern pulled its intranasal flu vaccine from the market in 2001, for example, after it found it increased the risk of temporary facial paralysis.

A product called FluMist, a live attenuated intranasal influenza vaccine approved in the United States and Europe, is superior to the intramuscular version in young children1. Adults may also find it more convenient to get a nasal spray vaccine, rather than an injection. But FluMist didn’t work as well in adults. This is because many have had years to build up some immunity to flu viruses. Even if this immunity is not strong enough to prevent the disease, the mucosal immune responses of adults can prevent the weakened vaccine from infecting nasal cells or clear it before it can do its job.

“It’s a balancing act between making sure the vaccine doesn’t cause disease and yet it’s repeated enough to induce mucosal immunity in people who have had some experience with the virus,” says Kanta Subbarao, director of the World Health Organization (WHO) Collaborator. Influenza Reference and Research Center in Melbourne, Australia. Researchers do not yet know whether this issue may also affect intranasal COVID-19 vaccines.

Where and when might the mucosal COVID-19 vaccines be available?

About 100 mucosal COVID-19 vaccines are in development worldwide, according to Airfinity, a health analytics company in London (see “Mucosal COVID-19 Vaccines”). About 20 of them have reached human clinical trials, of which at least four — in India, Iran and two in China — have completed or are undergoing phase III studies to test safety and how well they work compared to others. vaccines. Iran gave emergency approval for its vaccine in October 2021, and at least five million doses have been delivered to the Ministry of Health, says Ali Es-haghi, an analytical chemist at the Razi Vaccine and Serum Research Institute in Karaj, which developed the vaccine. . But the institute has yet to publish data on effectiveness in humans.

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