Dog vaccine

From a sniff or a swallow, new vaccines aim to curb the spread of Covid-19

As the SARS-CoV-2 virus spreads, it changes. It helped him break through our firewalls, the immunity created by vaccines or left behind after we recovered from an infection. That’s why, well into the third year of the pandemic, we’re in the midst of another wave of Covid-19 caused by the most immune-evasive variant to date, BA.5. And more variations are coming.

Even as vaccine makers rush to update first-generation vaccines in hopes of fixing our fall protection, other scientists are taking a different approach, making vaccines delivered via nasal sprays or tablets that would deploy more immune defenders to the front of the body. wrinkles: the lining of the mouth, nose and throat.

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

If this works, it is hoped that mucosal immunity could slow the development of new coronavirus variants and finally bring the Covid-19 pandemic under control.

However, there is still a long way to go before that happens, and many scientists argue that the approach requires an injection of funds to accelerate the pace of development, similar to the billions of dollars doled out by the Operation Warp Speed ​​delivered the first generation of Covid-19 vaccines in record time.

Old-school approach meets new technology

The idea behind vaccinating the mucosa – the lining of the “tube” (as mucosal immunologists call it) that runs from our nose and mouth to our lungs and intestines – 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 older types of vaccine technology, using killed or weakened versions of a virus or bacteria to teach the body to recognize it and fight it off when a real infection strikes.

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

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

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

That might be about to change, though.

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More than a dozen nasal spray vaccines against Covid-19 are being tested worldwide. Many are using new kinds of technology, like delivering instructions to make the coronavirus spike protein through harmless Trojan horse viruses. Others aim to deploy the mRNA technology that has been so successful in injectable nasal spray vaccines.

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

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

“What we found was that if you did an oral immunization, you inhibited the ability of this breakthrough to infect other animals,” said Sean Tucker, chief scientific officer of Vaxart.

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 convey instructions for making parts of the pic SARS-CoV-2 protein in gut cells, which stimulates the release of antibodies in the nose and mouth.

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In an early trial that included 35 participants, 46% had an increase in antibodies in their nose after taking the pill vaccine. Those that did seemed to create a broad spectrum of immunity against a number of types of coronavirus, and they seemed to retain that protection for about a year. It may take a little longer than injectable vaccines, although more research is needed to confirm these findings.

Tucker presents these first results Monday at the Seattle conference. He says they will also be released as a pre-print study in the coming days.

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

Most mucosal vaccines in development are designed to be given as a squirt of liquid or a mist into the nose, and many are intended for use as boosters in people who have received a full primary series of Covid-19 vaccines. 19.

“I don’t think of them as 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 well.

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

Here's an overview of how the different coronavirus vaccines work

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

One such approach was recently tested by Akiko Iwasaki, an immunobiologist at Yale University. According to their preprint study, Iwasaki and his team inoculated mice with a low dose of Pfizer’s Comirnaty mRNA vaccine and followed two weeks later with an mRNA vaccine booster given by nasal spray. The low dose of the injected vaccine was intended 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.

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

Opt for IgA antibodies

Mucosal vaccines also target a slightly different part of the immune system than injections.

The injections prompt the body to make antibodies against the virus that causes Covid-19. Most of them are Y-shaped proteins called IgG antibodies that are programmed to recognize and block specific parts of the SARS-CoV-2 virus along its tips, the parts of the virus that latch on and infect our cells.

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

Like bouncers in a bar, IgA antibodies are the primary immune guarding molecules in the mucosa.

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

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

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

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

“It’s now a very contagious virus,” she said.

Iwasaki says she would like to get her vaccine out of animal studies and into human clinical trials.

“We are still at the stage where we are struggling to raise funds even to manufacture the vaccine for human use, because it takes millions of dollars, and we are not sitting on that kind of money for the laboratory of research,” she said. said, “so not yet.”