New nasal vaccine against Covid-19 shows potential after trials in Germany

Scientists in Germany say they have managed to produce a nasal vaccine that can stop a Covid-19 infection in the nose and throat, where the virus first establishes itself in the body.

In experiments with hamsters, two doses of the vaccine, which is made with a live but weakened form of the coronavirus, prevented the virus from copying itself in the animals’ upper airways – achieving so-called “sterilizing immunity” and preventing the disease.

While this vaccine has several other hurdles to overcome before reaching a doctor’s office or pharmacy, other nasal vaccines are already in use or nearing the end of clinical trials.

China and India rolled out vaccines administered through nasal tissues last year, though it’s not clear how well they are working.

Studies on the effectiveness of these vaccines have yet to be published, leaving the world to wonder whether this protective approach really works in people.

next generation vaccines

The United States has reached an impasse with Covid-19. Even with the darkest days of the pandemic behind us, hundreds of Americans still die daily as the infection lingers in the return to normal life.

As long as the virus continues to spread among people and animals, there is always the possibility that it could mutate into a more contagious or more harmful version of itself.

And while 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 vaccines, which aim to shut down the virus before it has a chance to make us sick and ultimately stop the infection from spreading, could make this respiratory infection less of a threat.

One way that scientists are trying to do this is by boosting mucosal immunity, bolstering the immune defenses in the tissues that line the upper airways, exactly where the virus would arrive and begin to infect our cells.

It’s a bit like putting firefighters on the smoke alarm in your home, says study author Emanuel Wyler, a scientist at the Helmholtz Association’s Max Delbruck Center for Molecular Medicine in Berlin.

The immunity created by the injections works throughout the body, but resides primarily in the blood. This means that it may take longer to provide a response.

“If they’re already there, they can put out the fire right away, but if they’re about two miles away, they first have to drive there, and by that time, a third of the house is already on fire,” Wyler related in an interview with CNN .

Mucosal vaccines are also better at preparing a different kind of response than injections. They work best by calling on IgA antibodies, which have four “arms” to grab invaders, rather than just the two “arms” that the “y”-shaped IgG antibodies have.

Some scientists understand that IgA antibodies can be less “picky” about their targets than IgG antibodies, which makes them better equipped to deal with new variants.

This nasal vaccine in question takes a new approach to a very old idea: weakening a virus so that it is no longer a threat and then giving it to people so that their immune systems learn to recognize and fight it.

The first vaccines with this approach date back to the 1870s, against anthrax and rabies. Back then, scientists weakened the agents they were using with heat and chemicals.

The researchers manipulated the genetic material of the virus to make it difficult for the cells to translate. This technique, called codon pair deoptimization, makes it possible for the virus to be identified by the immune system without making the body sick.

“Can you imagine reading a text… and each letter is a different font, or each letter is a different size, so the text is much harder to read. And that’s basically what we do in codon pair deoptimization,” Wyler explained in an interview with CNN .

Promising results in animal studies

In studies of hamsters, published Monday in the journal Nature Microbiology, two doses of the nasal vaccine that uses the live but weakened form of the virus created a much stronger immune response than two doses of a vaccine based on hamsters. mRNA or one that uses an adenovirus to carry vaccine instructions into cells.

The researchers think that the “live” but weakened vaccine probably worked better because it closely mimics the process of a natural infection.

Nasal vaccine also introduces the whole coronavirus to the body, not just its proteins spikeas do current Covid-19 vaccines, so the hamsters were able to manufacture “immunological weapons” against a wider range of targets.

As promising as all this sounds, vaccine experts stress that caution is needed. That immunizer still needs to go through more tests before it’s ready for use, but they point out that the results so far look encouraging.

“They did a really cool job. This is obviously a competent and caring team who have done this job and impressive in the scope of what they have done. Now 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 research in question.

The study started in 2021, before the Omicron variant existed, so the vaccine tested in these experiments was made with the original strain of the virus.

In experiments, when they infected animals with Omicron, the weakened “live” nasal vaccine still performed better than the others, but its ability to neutralize the virus was diminished. Researchers think it will need an update.

Immunizane also needs to be tested in humans, and Wyler says they are working on that. The scientists reported that they have partnered with a Swiss company called RocketVax to begin phase one clinical trials.

Other vaccines are further along, but progress has been “slow and hesitant,” Poland noted. The groups working on these vaccines are fighting to raise the high costs of getting a new immunizer to market, and they are doing so in an environment where people think this race is won and done.

In reality, we are far from that, pondered Poland. All it takes is another Ômicron-level shift in the evolution of the virus and we could be back to square one, without tools against the coronavirus.

“That’s silly. We should be developing a pan-Coronavirus vaccine that induces mucosal immunity and is long-lasting,” she warned.

Other immunizations in development

At least four nasal vaccines for Covid-19 have reached the final stage of testing in people, according to the World Health Organization’s (WHO) vaccine tracker.

Nasal vaccines already in use in China and India rely on harmless adenoviruses to carry their instructions into cells, although efficacy data for them has not been published.

Two other nasal immunizers are nearing completion in human studies.

One, a recombinant vaccine that can be produced cheaply in chicken eggs, like many flu vaccines, is being tested by researchers at Mount Sinai in New York City.

Another, like the German vaccine, uses a live but weakened version of the virus. It is being developed by a company called Codagenix. The results of these studies, which were carried out in South America and Africa, may come out later this year.

The German team says they are anxiously watching the Codagenix data. “They will be very important for us to know where this type of attempt is basically promising or not”, highlighted Wyler.

But they have reason to be concerned. Respiratory infections have proven difficult targets for inhaled vaccines.

FluMist, which uses a live but weakened form of the flu virus, works reasonably well in children but is not as helpful in adults. The reason is thought to be that adults already have an immune memory for the flu, and when the virus is injected into the nose, the vaccine mostly boosts what’s already there.

Still, some of the most potent vaccines, like measles, mumps and rubella, use live attenuated viruses, so it’s a promising approach.

Another consideration is that “live” vaccines cannot be taken by everyone. People with very compromised immunity are often warned against using live vaccines because even these very weakened viruses can be risky for them.