Nose Spray Vaccines Could Quash COVID Virus Variants

The relentless evolution of the COVID-causing coronavirus has taken a bit of the shine off the vaccines developed during the first year of the pandemic. Versions of the virus that now dominate circulationOmicron and its subvariants—are more transmissible and adept at evading the body’s immune defenses than its original form. The current shots to the arm can still prevent serious illness, but their ability to ward off infection completely has been diminished. And part of the reason may be the location of the jabs, which some scientists now want to change.

To block infections entirely, scientists want to deliver inoculations to the site where the virus first makes contact: the nose. People could simply spray the vaccines up their nostrils at home, making the preparation much easier to administer. There are eight of these nasal vaccines in clinical development now and three in phase 3 clinical trials, where they are being tested in large groups of people. But making these vaccines has proven to be slow going because of the challenges of creating formulations for this unfamiliar route that are both safe and effective.

What could be most important about nasal vaccines is their ability to awaken a powerful bodily defender known as mucosal immunity, something largely untapped by the standard shots. The mucosal system relies on specialized cells and antibodies within the mucus-rich lining of the nose and other parts of our airways, as well as the gut. These elements move fast and arrive first, stopping the virus, SARS-CoV-2, before it can create a deep infection. “We are dealing with a different threat than we were in 2020,” says Akiko Iwasaki, an immunologist at Yale University. “If we want to contain the spread of the virus, the only way to do that is through mucosal immunity.

Iwasaki is leading one of several research groups in the U.S. and elsewhere that are working on nasal vaccines. Some of the sprays encapsulate the coronavirusspike proteins—the prominent molecule that the virus uses to bind to human cells—into tiny droplets that can be puffed into the sinuses. Others add the gene for the spike to harmless versions of common viruses, such as adenoviruses, and use the defanged virus to deliver the gene into nasal tissue. Still others rely on synthetically bioengineered SARS-CoV-2 converted into a weakened form known as a live attenuated vaccine.


How to Make Tumor Eliminate Itself

A new technology developed by University of Zurich (UZH) researchers in Switzerland enables the body to produce therapeutic agents on demand at the exact location where they are needed. The innovation could reduce the side effects of cancer therapy and may hold the solution to better delivery of Covid-related therapies directly to the lungs.

Scientists have modified a common respiratory virus, called adenovirus, to act like a Trojan horse to deliver genes for cancer therapeutics directly into tumor cells. Unlike chemotherapy or radiotherapy, this approach does no harm to normal healthy cells. Once inside tumor cells, the delivered genes serve as a blueprint for therapeutic antibodies, cytokines and other signaling substances, which are produced by the cancer cells themselves and act to eliminate tumors from the inside out.

Imaris Snapshot

View of the tumor from the inside. A piece of the tumor was made completely transparent and scanned in 3D with a special microscope. The components labeled with fluorescent colors were rendered in a rotatable 3D representation on the computer (red: blood vessels, turquoise: tumor cells, yellow: therapeutic antibody)

We trick the tumor into eliminating itself through the production of anti-cancer agents by its own cells,” says postdoctoral fellow Sheena Smith, who led the development of the delivery approach. Research group leader Andreas Plückthun explains: “The therapeutic agents, such as therapeutic antibodies or signaling substances, mostly stay at the place in the body where they’re needed instead of spreading throughout the bloodstream where they can damage healthy organs and tissues.”

The UZH researchers call their technology SHREAD: for SHielded, REtargetted ADenovirus. It builds on key technologies previously engineered by the Plückthun team, including to direct adenoviruses to specified parts of the body to hide them from the immune  system. With the SHREAD system, the scientists made the tumor itself produce a clinically approved breast cancer antibody, called trastuzumab (Herceptin®), in the mammary of a mouse. They found that, after a few days, SHREAD produced more of the antibody in the tumor than when the drug was injected directly. Moreover, the concentration in the bloodstream and in other tissues where side effects could occur were significantly lower with SHREAD. The scientists used a very sophisticated, high-resolution 3D imaging method and tissues rendered totally transparent to show how the therapeutic antibody, produced in the body, creates pores in blood vessels of the tumor and destroys tumor cells, and thus treats it from the inside.