With the spread of the SARS-CoV-2 virus, it is changing. It has helped bypass our firewalls, the immunity generated by vaccines or left in after recovering from an infection. That’s why, in the third year of the pandemic, we’re in the midst of another wave of Covid-19 caused by the most elusive variant of immunity to date, BA 5. And more variants to come.
Even as vaccine manufacturers race to update first-generation shots in hopes of tinkering with our fall protection, other scientists are taking a different approach, delivering vaccines via nasal sprays or tablets that would spread more immune defenders up the front of the body. Lines: the lining of the mouth and nose and larynx.
“The hope is to strengthen the defenses in the nose so that the virus does not multiply in the nose,” said Dr. Elaine Foxman, an immunobiologist at Yale University School of Medicine. “So someone who has had a really effective mucosal vaccine cannot support virus replication or make viruses that can infect other people.
There is a long way to go before that happens, however, and many scientists say the approach needs to pump in funding to speed development, just as billions of dollars spent through Operation Warp Speed provided the first generation of Covid-19 vaccines. in record time.
Old approach meets new technology
Most rely on the oldest type of vaccine technology, using dead or weakened copies of a virus or bacteria to teach the body how to recognize and fight it when a real infection occurs.
Because of those actual pathogens, some people cannot use this type of vaccine. It’s dangerous to expose certain groups — including pregnant women and those with compromised immune systems — even to weakened viruses.
None of them have achieved the goal of preventing transmission, but it may be because they are not getting the same kind of investment as injectable vaccines, says Ed Laville, an immunologist at Trinity College Dublin.
“What hasn’t really happened with mucosal vaccines is the kind of huge advance in technology that happened with injectable vaccines, even before Covid,” Laville said.
This may be about to change, though.
Can nasal spray vaccines curb the new variables?
More than a dozen nasal spray vaccines against Covid-19 are being tested worldwide. Many are using new types of technologies, such as providing instructions for making a coronavirus spike protein through harmless Trojans. Others aim to spread the mRNA technology that has been so successful in injectable vaccines as a nasal spray.
One company, Vaxart, has even made a tablet that delivers instructions for making parts of the novel coronavirus into the gut, which then builds immunity in the “tube.”
“What we’ve found is that if you do an oral vaccination, you dampen the ability of that penetration to infect other animals,” said Sean Tucker, Vaxart’s chief scientific officer.
The Vaxart tablet, which is the size and shape of aspirin, uses adenoviruses — the same delivery system used by the Johnson & Johnson and AstraZeneca Covid vaccines — to transmit instructions for making parts of the SARS-CoV-2 spike protein that turns into cells in the gut, stimulating the secretion of antibodies in the nose and mouth.
In an early trial with 35 participants, 46% had an increase in antibodies in their nose after taking the tablet vaccine. Those who did appear to have created a wide range of immunity to a number of coronavirus types, and they seemed to stick to that protection for about a year. This may be a bit longer than injectable vaccines, although more research is needed to confirm these results.
Tucker will present these early results Monday at the Seattle conference. He says it will also be published as a preprint study in the coming days.
Tucker says a phase two trial of a tablet with a slightly different composition, involving nearly 900 participants, is also underway. It is scheduled to be completed next summer.
Most mucosal vaccines in development are designed to be delivered as a liquid mist or nasal spray, and many are intended for use as boosters in people who have had a full initial series of Covid-19 vaccines.
“I don’t consider them to be nasal vaccines. I think they enhance the nose,” said Jennifer Gummerman, an immunologist at the University of Toronto who specializes in tissue-specific immunity.
This is important, Gummerman says, because nasal vaccines — such as FluMist — haven’t really worked well.
She says the next generation of vaccinations will be something different. They will build on the body’s immunity created by the shots; She says they will redeploy it in the nose and throat where it is most needed.
“But here, we’re actually talking about something else, where we’re talking about building on the systemic immunity that was induced by a three-shot mRNA vaccine and then training that systemic immunity to travel to the upper respiratory tract by way of through the nose,” Gummerman says.
Only the group that got the injection followed by the nasal spray developed a strong immunity to the Covid-19 virus.
“This approach that we demonstrated in a mouse model is 100% protective against the lethal dose of SARS-CoV-2 infection, and significantly reduces viral load in the nose and lung,” Iwasaki said.
Go for IgA antibodies
Mucosal vaccines also target a slightly different part of the immune system than injections.
The injections stimulate the body to make antibodies to the virus that causes Covid-19. Most of them are Y-shaped proteins called IgG antibodies that are programmed to recognize and prevent specific parts of the SARS-CoV-2 virus along its mutations, the parts of the virus that stick to and infect our cells.
A much smaller portion of these are IgA antibodies, Gummerman says, and the two pieces of Y seem to be attached together in their tails and turned laterally so that they look more like a dog bone.
Like the guards in the pub, IgA antibodies are the primary immune molecules that protect in the mucosa.
These molecules are bulkier than IgG antibodies. They have four arms instead of two, and they are special because they are less selective about what they catch on IgG antibodies.
“They may be more mixed in the way they learn about the different variables,” Gummerman said. “And that’s obviously a plus.”
The shots increase IgA antibodies in the nose for a short time, but the hope is that the mucus shots will increase the number of these guards and help them stay active for longer.
“Whether they’re able to confer complete sterilization immunity is a very difficult task,” Gummerman said. “But we must now work on ways to slow down transmission from person to person, because this virus keeps mutating and then tricks our immune system and bypasses that mucous layer.
“This is a highly contagious virus now,” she said.
Iwasaki says she’d like to move her vaccine from animal studies to human clinical trials.
“We’re still at the point where we’re struggling to raise money, even make a vaccine for human use, because it takes millions of dollars, and we’re not allocating that kind of money to a research lab,” he said, “not yet.”