Omicron 5, how do we defeat it? The role of mucosal immunity in closing the virus gate

Existing vaccines licensed by international regulatory bodies, from the US Food and Drug Administration to the EMA for Europe, have shown that they can ensure protection in the face of the dangerous disease caused by Covid. Even with the new variants Omicron 4 and 5 in place. What they fail to provide is a wall of infection. The virus continues to spread faster and faster, forcing many people at home to have a fever, sore throat and cough. How then stop the high transmission capacity shown by the Omicron 5? And how to be prepared in case there are new, possibly more contagious variants? Science works on different paths. As a first step, drug companies have focused on updating existing vaccines that will likely see the light of day next fall. However, these new boosters, both Pfizer and Moderna, are built on the basis of the Omicron 1 and 2 variant and do not seem to promise the same results against Omicron 5. In parallel, a super vaccine is being worked on against all coronaviruses, which may allow you in The future is challenged by all the variants of Covid that will emerge. Finally, an effective solution to prevent infection is being studied. How? Follow up on the role of mucosa in immunity.

Nasal spray vaccine to stop infection

As mentioned, current vaccines (in the arm) are still able to prevent serious diseases, but their ability to completely ward off infection has declined. Part of the reason may be where the drug is injected, which some scientists now want to change. To stop infection completely, scientists want to give the vaccine where the virus comes in contact first — the nose. People can simply get the vaccines in their nose at home, which makes preparation much easier. There are currently eight nasal vaccines in clinical development and three in phase III clinical trials, tested on large groups of people. But production has proven to be slow due to the challenges of creating safe and effective formulations of this unknown pathway.

mucosal immunity

What may be even more important than nasal vaccines is their ability to awaken a powerful defender of the body known as mucosal immunity, something that current vaccines have largely underutilized. The mucosal system relies on specialized cells and antibodies within the mucus-rich lining of the nose and other parts of the airways, as well as the intestines. These items move quickly and arrive first, stopping the virus before it can cause 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 that is through mucosal immunity.”

Guard at the entrance

Iwasaki leads one of several research groups in the United States and around the world working on nasal vaccines. Some sprays encapsulate coronavirus proteins, the prominent molecule the virus uses to bind human cells, into tiny droplets that can swell into your sinuses. Others add the gene for spike to harmless versions of common viruses, such as adenoviruses, and use the denatured virus to deliver the gene to nasal tissues. Still others rely on the bioengineered SARS-CoV-2 and convert it into 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 so-called immunoglobulin G (IgG) antibodies. They spread in the bloodstream and patrol the virus. The nasal sprays collect a separate group of antibodies known as immunoglobulin A (IgA). This spongy tissue fills the mucous membrane of the nose, mouth and throat, where the Covid-19 coronavirus first lands. Iwasaki likens mucous vaccines to placing a guard at the front door, rather than waiting for the invader to actually be inside to attack.

antibody response

While conventional vaccines are generally weak at inducing protective immunity to the mucosa, nasal vaccines have been shown to do a good job of inducing both mucosal and systemic responses. Last year, researchers from the National Institutes of Health conducted a side-by-side comparison of intramuscular administration of the Oxford-AstraZeneca vaccine. They found that hamsters who received the vaccine through the nose had higher levels of SARS-CoV-2 antibodies in their blood than those who received it through the muscles. The University of Oxford is now testing the intranasal vaccination in a phase I study, which will assess the vaccine’s safety in a small number of people. However, the development of an intranasal vaccine is complicated, because scientists know relatively little about the mechanisms of mucosal immunity. “While the human immune system is a black box, the mucosal immune system is perhaps the blackest of all,” says epidemiologist Wayne Cove, CEO and founder of the Human Vaccine Project, a public-private partnership aimed at accelerating vaccine development.

How to get the spray vaccine

And while spraying seems like a simpler way to dispense with a shot, in practice that is not the case. By intramuscular injection, the needle delivers vaccine components directly into the muscle, where they rapidly encounter resident immune cells. On the other hand, the nebulizer should work its way into the nasal cavity without sneezing. So these components must penetrate the thick mucus barrier and activate the immune cells that are locked inside. Not everyone does.

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