Sniff or swallow, new vaccines aim to slow the spread of Covid-19 – WSVN 7News | Miami News, Weather, Sports

(CNN) – Vaccines injected against the coronavirus that causes Covid-19 have been wildly successful, saving nearly 20 million lives worldwide in their first year of use and reducing the number of deaths from the pandemic by about one year. 63%, according to a recent study. However, as good as these vaccines are, they have not stopped the virus from spreading from person to person.

As the SARS-CoV-2 virus spreads, it changes. That helped get past our firewalls, the immunity created by vaccinations or left over after we recover from an infection. That is why, well into the third year of the pandemic, we are in the midst of another wave of Covid-19 caused by the most immunoevasive variant so far, BA.5. And more variants are coming.

Even as vaccine makers scramble to update first-generation shots in hopes of improving our protection for the fall, other scientists are taking a different approach, having vaccines delivered through nasal sprays or tablets that would deploy more immune defenders to the front of the body. lines: the lining of the mouth, nose, and throat.

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

“That would be like the holy grail,” said Foxman, who helped plan this week’s International Congress of Mucosal Immunology meeting in Seattle, sponsored by drug companies Pfizer, Janssen and Merck.

If it works, there is hope that mucosal immunity could slow the development of new coronavirus variants and ultimately bring the covid-19 pandemic under control.

However, there is a long way to go before that happens, and many scientists say the approach needs an infusion of funding to speed up the pace of development, much like the billions of dollars doled out for Operation Warp Speed. They delivered the first generation of vaccines against Covid-19 in record time.

An old approach meets new technology
The idea behind vaccinating the mucosa, the lining of the “tube” (as mucosal immunologists call it) that runs from the nose and mouth to the lungs and intestine, is not new. There are nine vaccines that work this way, including oral drops that protect against polio, cholera, salmonella, and rotavirus, and a nasal spray, FluMist, that inoculates against the flu.

Most are based on the older types of vaccine technologies, using killed or weakened versions of a virus or bacteria to teach the body how to recognize and fight it when a real infection starts.

Due to these real pathogens, some people cannot use these types of vaccines. It is risky to expose certain groups, including pregnant women and people with weakened immune systems, even to weakened viruses.

None have achieved the goal of blocking the transmission of an infection, but that may be because they haven’t received the same kind of investment as injectable vaccines, says Ed Lavelle, an immunologist at Trinity College in Dublin.

“What hasn’t really happened with mucosal vaccines is the great technological advances that have happened with injectable vaccines, even before Covid,” Lavelle said.

However, that may be about to change.

Can nasal spray vaccines stop new variants?
More than a dozen nasal spray vaccines against Covid-19 are being tested around the world. Many use new kinds of technologies, such as delivering instructions to make the coronavirus spike protein via harmless Trojan horse viruses. Others aim to implement the mRNA technology that was so successful in injectable nasal spray vaccines.

One company, Vaxart, has even made a tablet that provides instructions for making parts of the new coronavirus in the gut, which then builds immunity in “the tube.”

In animal tests, hamsters vaccinated in the nose or mouth are less likely to spread a SARS-CoV-2 infection to uninfected animals that are in separate cages but share the same air.

“What we found is that if you did an oral immunization, you inhibited that lead’s ability to infect other animals,” said Sean Tucker, Vaxart’s chief scientific officer.

The Vaxart tablet, which is about the size and shape of an aspirin, uses an adenovirus – the same delivery system used by Johnson & Johnson and AstraZeneca Covid vaccines – to carry instructions for converting parts of the SARS- CoV-2 on cells in the intestine, which stimulates the release of antibodies in the nose and mouth.

In an early trial of 35 participants, 46% had a rise in antibodies in their nose after receiving the tablet vaccine. Those that did appeared to create a broad spectrum of immunity to various types of coronavirus, and seemed to maintain that protection for about a year. That may be slightly longer than injectable vaccines, although more research is needed to confirm those results.

Tucker will present these first results on Monday at the Seattle conference. He says that they will also be published as a preprint study in the next few days.

A phase 2 trial of a tablet with a slightly different formulation is also underway, involving nearly 900 participants, Tucker says. It is scheduled to be completed next summer.

Most of the mucosal vaccines in development are designed to be administered as a liquid squirt or spray into the nose, and many are intended to be used as boosters in people who have received a full primary series of COVID-19 vaccines.

“I don’t consider them nasal vaccines. I think of them as nasal boosters,” said Jennifer Gommerman, an immunologist at the University of Toronto who specializes in tissue-specific immunity.

That’s important, Gommerman says, because nasal vaccines, like FluMist, haven’t really worked that well.

The next generation of vaccines will be something different, she says. They will rely on the whole body immunity created by the injections; they’ll just redeploy it to the nose and throat where it’s needed most, she says.

“But here, we’re actually talking about something else, where we’re talking about building up the systemic immunity that was induced by a vaccine to three injections of mRNA and then training that systemic immunity to go to the upper respiratory tract by propelling it through the nose,” Gommerman says.

One such approach was recently tested by Akiko Iwasaki, an immunobiologist at Yale University. According to her preprint study, Iwasaki and her team inoculated mice with a low dose of Pfizer’s Comirnaty mRNA vaccine and followed up two weeks later with a booster of the mRNA vaccine administered via nasal spray. The low dose of the injected vaccine was meant to simulate waning immunity. Other groups of mice received only one injection or only one dose of vaccine in the nose.

Only the group that received the injection followed by the nasal spray developed robust immunity against the Covid-19 virus.

“That approach that we have shown in the mouse model is 100% protective against the lethal dose of SARS-CoV-2 infection, and dramatically reduces the viral load in the nose and in the lung,” Iwasaki said.

Looking for IgA antibodies
Mucosal vaccines also target a slightly different part of the immune system than injections.

The injections cause 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 their spikes, the parts of the virus that attach to and infect our cells.

A much smaller portion of these are IgA antibodies, and they look like two Y’s joined at their tails and turned sideways to look more like a dog bone, says Gommerman.

Like bouncers in a bar, IgA antibodies are the main immune molecules on guard in the mucosa.

These molecules are more robust than IgG antibodies. They have four arms instead of two, and they’re special because they’re less picky about what they grab than IgG antibodies.

“They could be a bit more promiscuous in how they recognize different variants. And that’s obviously an advantage,” Gommerman said.

The injections raise IgA antibodies in the nose for a short time, but the hope is that the mucosal vaccines will actually increase the population of these sentinels and help them stay active longer.

“If they will be able to confer complete sterilizing immunity, that is a very difficult task,” said Gommerman. “But now we should be working on ways to slow down person-to-person transmission, because this virus continues to mutate and then it tricks our immune system and breaks through that mucous layer.

“This is now a very contagious virus,” he said.

Iwasaki says he would love to get his vaccine out of animal studies and into clinical trials in people.

“We’re still at the stage where we’re struggling to raise money, even make the vaccine for human use, because millions of dollars are needed, and we’re not sitting around with that kind of money for the research lab,” he said. he said, “so not yet”.

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