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German scientists say they have succeeded in making a nasal vaccine capable of stopping Covid-19 infection in the nose and throat, where the virus first takes its foothold in the body.
In experiments on hamsters, two doses of the vaccine – made with a live but weakened form of the coronavirus that causes Covid-19 – prevented the virus from copying itself into the animals’ upper respiratory tract, thereby achieving “sterilizing immunity” and preventing disease. , a goal long sought by the pandemic.
Although this vaccine still has several hurdles to clear before reaching a doctor or pharmacy, other nasal vaccines are in use or nearing the finish line in clinical trials.
China and India both rolled out nasally administered vaccines last fall, although it’s unclear how well they work. Studies on the effectiveness of these vaccines have not yet been published, leaving much of the world wondering whether this approach to protection actually works in humans.
The United States is in something of an impasse with Covid-19. Even though the darkest days of the pandemic are behind us, hundreds of Americans are dying every day as the infection continues to simmer as we return to normal life.
As long as the virus continues to spread among humans and animals, there is always a risk of mutating into a more contagious or damaging version of itself. And even though Covid infections have become manageable for most healthy people, they can still pose a danger to vulnerable groups such as the elderly and the immunocompromised.
Researchers hope that next-generation Covid-19 vaccines, which aim to stop the virus before it has the chance to make us sick and ultimately prevent the spread of infection, could make our new resident respiratory infection less threatening.
Scientists are trying to do this by boosting mucosal immunity, boosting immune defenses in the tissues that line the upper respiratory tract, where the virus would land and start infecting our cells.
It’s a bit like stationing firefighters under the smoke detector in your house, explains study author Emanuel Wyler, a scientist at the Max Delbruck Center for Molecular Medicine of the Helmholtz Association in Berlin.
The immunity created by the injections works throughout the body, but it resides primarily in the blood. This means that preparing a response may take longer.
“If they are already there, they can immediately eliminate the fire, but if they are about 3 km away, they must first drive there, and at that time a third of The house is already on fire.” Wyler said.
Mucosal vaccines are also more effective than injections in preparing a different type of first responder. They are more successful at summoning IgA antibodies, which have four arms to latch onto invaders instead of the two arms that Y-shaped IgG antibodies have. Some scientists think that IgA antibodies might be less choosy about their targets than IgG antibodies, which would make them better equipped to deal with new variants.
The new nasal vaccine takes a new approach to a very old idea: weakening a virus so that it no longer poses a threat, then giving it to people so their immune systems can learn to recognize and fight it. The first vaccines using this approach date from the 1870s, against anthrax and rabies. Back then, scientists weakened the agents they used with heat and chemicals.
Researchers manipulated the virus’s genetic material to make it harder for cells to translate. This technique, called codon pair deoptimization, hinders the virus so that it can be presented to the immune system without making the body sick.
“You could imagine reading a text… and each letter has a different font, or each letter has a different size, then the text is much more difficult to read. And that’s essentially what we do in codon pair deoptimization,” Wyler said.
In the hamster studies, published Monday in the journal Nature Microbiology, two doses of the live but weakened nasal vaccine created a much stronger immune response than two doses of an mRNA-based vaccine or a vaccine using a adenovirus to transport the vaccine. instructions in the cells.
Researchers believe the weakened live vaccine probably worked better because it closely mimics the process of a natural infection.
The nasal vaccine also previews the entire coronavirus for the body, not just its spike proteins as current Covid-19 vaccines do, so the hamsters were able to build immune weapons against a wider range of targets.
As promising as this may sound, vaccine experts say caution is warranted. This vaccine still needs to pass further testing before it is ready for use, but the results appear encouraging.
“They did a very good job. It is obviously a competent and thoughtful team which carried out this work, and impressive by the scale of what they have done. It just needs to be repeated,” perhaps in primates and certainly in humans before it can be widely used, said Dr. Greg Poland, who designs vaccines at the Mayo Clinic. He was not involved in the new research.
The study began in 2021, before the appearance of the Omicron variant, so the vaccine tested in these experiments was made with the original strain of the coronavirus. In experiments, when they infected animals with Omicron, the live but weakened nasal vaccine still performed better than the others, but its ability to neutralize the virus was diminished. Researchers think it will need an update.
It also needs to be tested on humans, and Wyler says they’re working on it. The scientists have partnered with a Swiss company called RocketVax to launch phase I clinical trials.
Other vaccines are further along, but progress has been “slow and halting,” Poland said. The groups working on these vaccines are struggling to raise the high costs of bringing a new vaccine to market, and they’re doing so in a context where people tend to think the vaccine race is won and over.
In reality, says Poland, we are far from it. All it would take is one more Omicron-level change in the evolution of the virus, and we could be back to square one, without effective tools against the coronavirus.
“That’s stupid. We should develop a pan-coronavirus vaccine that induces mucosal immunity and lasts for a long time,” he said.
At least four nasal Covid-19 vaccines have reached advanced stages of testing in humans, according to the World Health Organization’s vaccine tracker.
Nasal vaccines used in China and India rely on harmless adenoviruses to deliver their instructions to cells, although data on their effectiveness has not been published.
Two other nasal vaccines are completing human studies.
The first, a recombinant vaccine that can be produced inexpensively from chicken eggs, as many flu vaccines are, is being tested by researchers at Mount Sinai in New York.
Another, like the German vaccine, uses a live but weakened version of the virus. It is developed by a company called Codagenix. The results of these studies, carried out in South America and Africa, could be known later this year.
The German team says it is eagerly monitoring the Codagenix data.
“They will be very important in knowing whether this type of attempt is fundamentally promising or not,” Wyler said.
They have reason to worry. Respiratory infections have proven to be difficult targets for inhaled vaccines.
FluMist, a live but attenuated form of the flu virus, works reasonably well in children but doesn’t help adults as much. The reason is thought to be that adults already have an immune memory against the flu and when the virus is injected into the nose, the vaccine mainly reinforces what is already there.
Yet some of the most powerful vaccines, such as those for measles, mumps and rubella, use live attenuated viruses. This is therefore a promising approach.
Another consideration is that live vaccines cannot be given to everyone. People with very weakened immunity are often advised against using live vaccines, as even these very weakened viruses can pose a risk to them.
“Although it is highly attenuated, it is still a real virus,” Wyler said, so it will need to be used with caution.
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