Research Team Develops Inhalable COVID-19 ‘Vaccine’

A team of researchers has developed an inhalable COVID-19 vaccine, the Yale School of Engineering & Applied Science says.

“It also opens the door to delivering other messenger RNA (mRNA) therapeutics for gene replacement therapy and other treatments in the lungs,” the department writes.

The research team published its results in an article titled “Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination.”

Inhalable mRNAs will make vaccines, such as those against covid-19, more effective and may boost treatments for conditions like cystic fibrosis and asthma https://t.co/KpwHGIJn82

— New Scientist (@newscientist) August 16, 2023

It’s a dangerous development for individuals who want nothing to do with mRNA nanotechnology.

“The chances that this tech will be used on people without their consent and without their knowledge are extremely high,” Raw Egg Nationalist wrote.

Researchers have now found a way to deliver mRNA vaccines using inhalable nanoparticles in an aerosolised spray. The chances that this tech will be used on people without their consent and without their knowledge are extremely high. pic.twitter.com/sdHL2MJqHl

— RAW EGG NATIONALIST (@Babygravy9) August 21, 2023

The study results are published in Science Translational Medicine.

From the study’s abstract:

An inhalable platform for messenger RNA (mRNA) therapeutics would enable minimally invasive and lung-targeted delivery for a host of pulmonary diseases. Development of lung-targeted mRNA therapeutics has been limited by poor transfection efficiency and risk of vehicle-induced pathology. Here, we report an inhalable polymer-based vehicle for delivery of therapeutic mRNAs to the lung. We optimized biodegradable poly(amine-co-ester) (PACE) polyplexes for mRNA delivery using end-group modifications and polyethylene glycol. These polyplexes achieved high transfection of mRNA throughout the lung, particularly in epithelial and antigen-presenting cells. We applied this technology to develop a mucosal vaccine for severe acute respiratory syndrome coronavirus 2 and found that intranasal vaccination with spike protein–encoding mRNA polyplexes induced potent cellular and humoral adaptive immunity and protected susceptible mice from lethal viral challenge. Together, these results demonstrate the translational potential of PACE polyplexes for therapeutic delivery of mRNA to the lungs.

From the @SaltzmanLab, an inhalable vaccine that not only protects against the COVID virus, but opens the door for other mRNA therapeutics for gene replacement therapy and other treatments in the lungs. https://t.co/83IG5kNnSl #YaleEngineering pic.twitter.com/cT67WKCnfc

— Yale School of Engineering & Applied Science (@YaleSEAS) August 16, 2023

The Yale School of Engineering & Applied Science writes:

For the vaccine, the researchers demonstrated that two intranasal doses of the treatment, made with nanoparticles carrying mRNA COVID vaccine, is effective in mice. It also demonstrates that an inhalable delivery system allows for minimally invasive and lung-targeted mRNA delivery, potentially applicable for numerous pulmonary diseases in addition to COVID.

It’s a significant advance since scientists have had trouble creating lung-targeted mRNA therapies. Typically, these therapies have had poor transfection efficiency – that is, only a small fraction of administered nucleic acids make it into cells that lead to expression of the encoded protein. Also, in the past, the nanoparticles that deliver the mRNA have caused inflammation and other problems. The Saltzman group got around this hurdle in part by using a nanoparticle made from poly(amine-co-ester) polyplexes, or PACE, a biocompatible and highly customizable polymer.

Saltzman previously worked with the lab of Akiko Iwasaki, Sterling Professor of Immunology, on what Iwasaki calls a “prime and spike” COVID vaccine delivery system. The “prime” half of the system involves injections of the mRNA vaccine into a muscle – the shot that millions of people have already received. These vaccinations were followed up with familiar spike proteins or spike mRNA that are derived from the coronavirus and are sprayed directly into the nose.

In their new study, the researchers showed that the shot isn’t necessary to provide protection.

“In the new report, there is no intramuscular injection,” said Saltzman, the Goizueta Foundation Professor of Biomedical Engineering, Chemical & Environmental Engineering & Physiology. “We just gave two doses, a prime and a boost, intranasally, and we got a highly protective immune response. But we also showed that, generally, you can deliver different kinds of mRNA. So it’s not just good for a vaccine, but potentially also good for gene replacement therapy in diseases like cystic fibrosis and gene editing. We used a vaccine example to show that it works, but it opens the door to doing all these other kinds of interventions.”

Without the protective casing of the nanoparticles, the mRNA would quickly deteriorate inside the body. However, developing a nanoparticle for lung-targeted therapies has been tricky. Other attempts to develop an inhalable delivery system for mRNA have met obstacles due to the type of material used for the nanoparticles.

“It’s been a challenge trying to take the lipid nanoparticle vaccine delivery systems and make them active through the nose as well,” Saltzman said. “One of the advantages we have is that the PACE polymer that we’re using seems to be much milder, and much better tolerated in the lung than lipid nanoparticles are.”

According to the researchers, the next step “is to test the delivery system for other therapeutic applications.”