The vaccines developed during the first year of the Pandemic have taken a bit of the shine off. The Omicron and its subvariants are more transmissible than the original form, and they are better at evading the body's immune defenses. The current shots to the arm can still prevent serious illness, but their ability to ward off infections has been diminished. Some scientists want to change the location of the jabs.

Scientists want to deliver inoculations to the nose to block infections entirely. The preparation was much easier if people spray the vaccines up their noses. There are eight of these vaccines in clinical development and three in phase 3 trials, where they are being tested in large groups of people. Making these vaccines has proven to be slow because of the challenges of creating a vaccine that is both safe and effective.

The ability to awaken a powerful bodily defender known as mucosal immunity is something that is largely unexplored by the standard shots. The mucus-rich lining of the nose and other parts of the airway are home to specialized cells and antibodies. Akiko Iwasaki, an immunologist, says that the threat is different than it was in 2020.

Iwasaki leads a research group that is working on a vaccine for the nose. Some of the sprays can be used to protect against the coronaviruses, which can be found in human cells. Others add the spike to harmless versions of common viruses, such as adenoviruses, and use the defanged virus to deliver the gene into nasal tissue. Others rely on synthetically bio engineered SARS-CoV-2 converted into a weakened form known as a live attenuated vaccine.

A type of immune response known as systemic immunity is created by the more familiar shots in the arm. They patrol for the virus in the bloodstream. There is a set of antibodies known as IgA. These are found in the nose, mouth and throat, where the COVID-causing coronaviruses first land. Iwasaki compares putting a guard at the front door to waiting until the invader is inside to attack.

While conventional vaccines are generally poor at inducing protective immunity, nasal vaccines have been shown to do a good job of triggering both. A side-by-side comparison of the delivery of the Oxford-AstraZeneca vaccine was conducted last year. They found that hamsters that received the vaccine through the nose had higher levels of antibodies in their blood than hamsters that received it through the muscle. The University of Oxford is testing the safety of a vaccine in a small group of people.

The human immune system is a black box, and scientists don't know much about the machinations of the mucosal immune system. Scientists know that they have to tread cautiously. Substance squirted up the nose could raise the risk of brain damage. There was a link between the vaccine and Bell's palsy in the early 2000s.

In practice, a spray is not an easier delivery method than a shot. The vaccine ingredients are delivered directly into the muscle by a needle. Without being sneezed out, sprays must make their way into the nose. The immune cells locked within have to be activated by those ingredients. Not all do. Altimmune stopped development of its vaccine after disappointing trial results.

Some vaccine developers are turning to weakened or attenuated viruses because they can get through the barrier. Two companies, Codagenix and Meissa Vaccines, have used synthetic biology to build an attenuated version of the novel coronaviruses containing hundreds of genetic changes that drastically reduce its ability to replicate. In a recent news release, the Codagenix team reported promising results of their vaccine, CoviLiv. The spray caused a strong immune response against the different strains of the disease. The vaccine trains the immune system to recognize all the viral proteins, not just the spike. The vaccine can provide broad long-term immunity in a very resistant context if all components of the virus are present. CoviLiv is moving on to advanced testing in people as part of the World Health Organization sponsored Solidarity Trial Vaccines.

There are more candidates that have made it into clinical trials. Iwasaki has created a spray that works as a booster to the standard shot. She calls it Prime and Spike because it starts with an injection of an mRNA or other COVID vaccine based on the spike. Researchers spray a mix of spike proteins into the nose to convert the first reaction into immunity. In a preprint study not yet published in a peer-reviewed scientific journal, her team found that their one-two-punch protected mice from severe COVID while also significantly reducing the amount of SARS-CoV-2 in the nose and lungs.

The researchers found that adding spike proteins from the coronaviruses to their spray caused a broad spectrum of antibodies. There is a push for a universal coronaviruses vaccine and the combination has the potential to defend against new coronaviruses.

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With no needles or needles, it could be possible to reach a lot more people. The real decision will be whether the vaccine stops infections and illness, and those results will be more important than ease of use, according to Koff.