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Omicron 5, how to defeat it? The role of mucosal immunity to close the gateway to the virus

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Omicron 5, how to defeat it?  The role of mucosal immunity to close the gateway to the virus
Written by aquitodovale

The current vaccines authorized by international regulatory bodies, from the American FDA to the EMA for Europe, have shown that they can guarantee protection in the face of the serious disease caused by Covid. Even in the presence of the new Omicron 4 and 5 variants. What they fail to provide is a wall to infection. The virus still circulates and does it faster and faster, forcing many people at home with fever, sore throat and cough. How then to stem the high transmission capacity shown by Omicron 5? And how to be ready in the event of new variants, perhaps even more contagious? Science is working on different tracks. As a first step, the pharmaceutical companies have concentrated on updating the current vaccines which will probably see light in the next autumn. However, these new boosters, both Pfizer and Moderna, are conceived on the basis of the Omicron 1 and 2 variant and do not seem to promise the same results against Omicron 5. In parallel, work is being done on a super vaccine against all coronaviruses, which in the future could allow you to challenge all the variants of Covid that will emerge. Finally, an effective solution is being studied to block the infection. How? Pursuing the role of mucosal immunity.

The nasal spray vaccine to stop the infection

As mentioned, current vaccines (in the arm) can still prevent serious diseases, but their ability to completely ward off infection has been reduced. And part of the reason may be the location where the drug is injected, which some scientists now want to change. To completely stop infections, scientists want to administer the vaccine at the site where the virus first comes into contact – the nose. People could simply get the vaccines in their nostrils in their home, making the preparation much easier to administer. There are currently eight nasal vaccines in clinical development and three in Phase 3 clinical trials, tested on large groups of people. But production has proved slow due to the challenges of creating formulations for this unknown path that are both safe and effective.

Mucosal immunity

What may be more important than nasal vaccines is their ability to awaken a powerful body defender known as mucosal immunity, something largely untapped by current vaccines. The mucosal system relies on specialized cells and antibodies within the mucus-rich lining of the nose and other parts of our airways, as well as the intestines. These elements move fast and arrive first, stopping the virus before it can create a deep infection. “We are dealing with a different threat than we were in 2020,” says Akiko Iwasaki, an immunologist at Yale University. “If we want to contain the spread of the virus, the only way to do it is through mucosal immunity.”

A guard at the entrance

Iwasaki leads one of several research groups in the United States and around the world that are working on nasal vaccines. Some of the sprays encapsulate the spike proteins of the coronavirus, the prominent molecule the virus uses to bind to human cells, into tiny droplets that can be swollen in the sinuses. Others add the gene for the spike to harmless versions of common viruses, such as adenoviruses, and use the defangled virus to deliver the gene into nasal tissue. Still others rely on synthetically bioengineered SARS-CoV-2 converted to a weakened form known as a live attenuated vaccine.

Vaccines injected into the arm create a type of immune response known as systemic immunity, which produces what are called immunoglobulin G (IgG) antibodies. They circulate in the bloodstream and patrol the virus. Nasal sprays assemble a separate set of antibodies known as immunoglobulin A (IgA). These populate the spongy tissues of the mucous membrane of the nose, mouth and throat, where the coronavirus that causes Covid lands for the first time. Iwasaki likens mucosal vaccines to putting a guard on the front door, instead of waiting for the invader to already be inside to attack.

The antibody response

While conventional vaccines are generally poor at inducing mucosal protective immunity, nasal vaccines have been shown to do a good job of triggering both mucosal and systemic responses. Last year, researchers from the National Institutes of Health conducted a side-by-side comparison of intranasal and intramuscular administration of the Oxford-AstraZeneca vaccine. They found that hamsters who received the vaccine through the nose had higher levels of antibodies to SARS-CoV-2 in their blood than those who received it through muscle. The University of Oxford is now testing intranasal vaccination in a Phase 1 study, which will evaluate the safety of the vaccine in a small number of people. Developing a nasal vaccine is complicated, however, because scientists know relatively little about the machinations of mucosal immunity. “While the human immune system is a black box, the mucosal immune system is probably the blackest of the black boxes,” says epidemiologist Wayne Koff, CEO and founder of the Human Vaccines Project, a public-private partnership aimed at accelerating vaccine development.

How to get the spray vaccine

And although a spray seems like a simpler method of delivery than a shot, in practice it is not. With intramuscular injections, a needle delivers the vaccine ingredients directly into the muscle, where they quickly encounter resident immune cells. Sprays, on the other hand, must make their way into the nasal cavity without being sneezed. So those ingredients have to breach a thick mucus barrier and activate the immune cells locked inside. Not everyone does.

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