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COVID: Just smelled or swallowed, the new vaccine aims to stop the spread

An injected vaccine against the coronavirus that causes COVID-19 has been a resounding success, saving nearly 20 million lives globally in its first year of use and reducing pandemic mortality, according to a recent study. epidemic causes an estimated 63%, according to a recent study. As good as these shots are, however, they don’t stop the virus from spreading from person to person.

As the SARS-CoV-2 virus spreads, it changes. That helped it get through our firewalls, immunity created by vaccines or left behind after we recovered from an infection. That is why, in the third year of the pandemic, we are in the midst of another wave of COVID-19 caused by the most immune avoidance variant, BA.5. And more variants are coming.

Even as vaccine makers race to update first-generation shots in the hope of protecting us from the fall, other scientists are taking a different approach, creating vaccines. -Please delivered via nasal spray or tablets will deploy more immune protection to the body’s way: the lining of the mouth, nose and throat.

A.5. In particular, BA.5 is similarly dominant in other countries where BA.2.75 has been detected.

Dr Ellen Foxman, an immunobiologist at the Yale School of Medicine, said: “The hope is to strengthen the defenses right in the nose so the virus can’t replicate in the nose.” “And then a person who gets a really effective mucosal vaccine can’t even really support viral replication or produce a virus that can infect other people.

Foxman, who helped plan this week’s International Congress on Mucosal Immunology in Seattle, sponsored by the pharmaceutical companies Pfizer, Janssen and Merck, said.

If it works, there is hope that mucosal immunity could slow the growth of novel coronavirus variants and eventually bring the COVID-19 pandemic under control.

However, there is still a long way to go before that happens, and many scientists say the approach needs to be funded to accelerate development, in the same way that the billions of dollars that were raised from the War. Warp Speed ​​epidemic delivered the first generation of COVID-19 Vaccine in record time.

OLD ACCESS TO NEW TECHNOLOGY

The idea behind vaccinating the mucosa — the lining of the “tube” (as immunologists call the mucosa) that runs from our nose and mouth to our lungs and intestines — is not new. There are nine vaccines currently available that work this way, including oral drops that protect against polio, cholera, salmonella, and rotavirus, and a nasal spray, FluMist, for flu shots.

Most are based on the oldest types of vaccine technology, using killed or weakened versions of a virus or bacteria to teach the body how to recognize and fight it when an infection hits. really going on.

Because of those actual pathogens, some people can’t get these vaccines. It is risky to expose certain groups of people – including pregnant women and those with weakened immune systems – to an even weakened virus.

Ed Lavelle, an immunologist at Trinity College in Dublin, said: “Nobody has achieved the goal of stopping the transmission of the infection, but that could be because they are not being invested in the same way as injectable vaccines. .

“What hasn’t really happened with mucosal vaccines is that a kind of big advance in technology has happened with injectable vaccines, even before Covid,” said Lavelle.

However, that could be about to change.

CAN NASAL SPRAY VACCINES BRAKE BRAKES ON THE NEW INVERTER?

More than a dozen nasal spray vaccines against COVID-19 are being tested around the world. Many use new types of technology, such as providing instructions to generate the coronavirus spike protein through harmless Trojan horse viruses. Others aim to implement the mRNA technology with great success in injectable vaccines in the form of a nasal spray.

One company, Vaxart, has even produced a tablet that provides instructions for making parts of the new coronavirus reach the intestines, then creating immunity in “tubes”.

In animal tests, hamsters vaccinated with their nose or mouth were less likely to transmit SARS-CoV-2 to uninfected animals kept in separate but shared cages.

Sean Tucker, Vaxart’s chief scientific officer, said: “What we found is that if you do an oral vaccination, you inhibit that breakthrough ability to infect other animals. .

The Vaxart tablet, which is about the size and shape of an aspirin tablet, uses an adenovirus — the same delivery system used by the Johnson & Johnson and AstraZeneca COVID vaccines — to give instructions for making its parts. SARS-CoV-2 spikes proteins into cells in the intestines, stimulating the release of antibodies in the nose and mouth.

In an initial trial that included 35 participants, 46% had an increase in antibodies in the nose after taking the pill vaccine. These people appear to have conferred a broad spectrum of immunity to some coronaviruses, and they appear to have retained that protection for about a year. That could take a little longer than an injectable vaccine, though more research is still needed to confirm those results.

Tucker will present these early results Monday at the Seattle conference. They will also be published as a preprint study in the coming days, he said.

Phase 2 trials of a slightly different formulation of tablets, involving nearly 900 participants, are also underway, Tucker said. It is scheduled for completion next summer.

Most mucosal vaccines in development are designed for delivery as a liquid spray or a nasal spray, and many are intended for use as boosters in people who have had enough vaccinations. major series of COVID-19 vaccines.

“I don’t think they’re nasal vaccines,” said Jennifer Gommerman, an immunologist at the University of Toronto who specializes in tissue-specific immunology.

That’s important, says Gommerman, because nasal vaccines — like FluMist — don’t really work well.

The next generation of preparations will be different, she said. They will build the body-wide immunity that has been created by the injections; they will just redeploy it to the nose and throat where it is needed most,” she said.

“But here we’re really talking about something else, where we’re talking about building vaccine-generated systemic immunity with three shots of mRNA and then training the immunity. that systemic fluid to reach the upper respiratory tract, says Gommerman.

Such an approach was tested recently by Akiko Iwasaki, an immunobiologist at Yale University. Following their previous study, Iwasaki and her team implanted mice with a low dose of Pfizer’s Comirnaty mRNA vaccine and followed up two weeks later with a booster of the vaccine mRNA delivered via nasal spray. Low doses of the vaccine are given to simulate weakened immunity. Other groups of mice received only or a single dose of vaccine in the nose.

Only the group that received the injection and then the nasal spray developed strong immunity against the COVID-19 virus.

“That approach that we showed in the mouse model is 100% protective against a lethal dose of SARS-CoV-2 infection, and it significantly reduces the viral load,” Iwasaki said. in the nose and in the lungs,” Iwasaki said.

LOOKING FOR A cure for IGA

The mucosal vaccine also targets a part of the immune system slightly differently than vaccination.

The injection triggers the body to produce antibodies against the virus that causes COVID-19. Most of these are Y-shaped proteins called IgG antibodies that are programmed to recognize and block specific parts of the SARS-CoV-2 virus along its spines, the parts of which the virus attaches to. and infect our cells.

A much smaller portion of these are IgA antibodies, and they look like two Ys joined together on the tail and turned to the side so they look more like dog bones, Gommerman says.

Like bouncers at a bar, IgA antibodies are the main protective immune molecules in the mucosa.

These molecules are more potent than IgG antibodies. They have four arms instead of two, and they are special because they are less picky about what they attach to than IgG antibodies.

“They can be a bit more promiscuous in the way they perceive different variations. And that’s obviously a plus,” says Gommerman.

Vaccination raises IgA antibodies in the nose for a short time, but the hope is that the mucosal vaccine will actually increase the population of these sentinels and keep them active for longer.

“Whether they can induce complete sterilization immunity or not, that is a very high order,” says Gommerman. “But now we should find ways to slow down human-to-human transmission, as this virus continues to mutate and then trick our immune system and get past that mucosa.

“This is a very contagious virus,” she said.

Iwasaki said she is keen to move her vaccine out of animal studies and human clinical trials.

“We’re still at a stage where we’re struggling to raise money, even create a vaccine for people, because it costs millions of dollars, and we’re not sitting in that kind of money for lab,” she said, “that’s not it yet.”

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