What’s the Deal With Covid-19 Nasal Sprays?
While all eyes are on Pfizer’s and Moderna’s injectable Covid-19 vaccine, researchers elsewhere are pursuing treatments that take a different route: up the nose. Scientists are hoping that the right molecules, spritzed into the nostrils via a nasal spray, could provide protection from Covid-19 infection, at least temporarily.
The nose isn’t the only path into the body for SARS-CoV-2, the virus that causes Covid-19, but it is a major one. Some cells in the nasal passages have high numbers of viral receptors compared to other cells in the body, which may also be the reason why people with Covid-19 tend to lose their sense of smell and taste. Now, multiple teams of scientists are looking for ways to block the virus from getting into nasal cells. Below is a look at how different teams are trying to do so, though there are many more teams working on similar research that aren’t mentioned here.
On November 5, scientists at Columbia University in New York published a preprint showing that their nasal spray, squirted into the noses of ferrets, prevented Covid-19 infection. The study was small — only six ferrets got the spray — and it has not yet been peer-reviewed, but the findings are promising. When the treated ferrets were put into a cage with another ferret with Covid-19 for 24 hours, they did not get infected.
The key molecule in that spray blocks the ability of SARS-CoV-2 to get into cells. It specifically targets the much-talked-about spike protein, which the virus uses to fuse with human cells and cause infection (and gives the coronavirus its “crown”-like appearance). The molecule in the nasal spray, a chain of fats and amino acids called a lipopeptide, sticks to the spike protein and prevents fusion — and therefore infection — from happening. Those scientists submitted their paper to the journal Science, where it will undergo peer review. (If you’re wondering “why ferrets?” it’s because they’re from a family of animals called mustelids that are highly susceptible to Covid-19. This family includes mink, millions of which have been culled as a result of the pandemic.)
Scientists at Stanford University have a different idea for a molecule to spritz up the nose: antibodies from chickens. Much like humans, chickens produce antibodies as part of the immune response to a pathogen. As Science reported on November 10, the researchers injected the SARS-CoV-2 spike protein into the chests of chickens, waited for them to lay eggs, harvested antibodies from the yolks, then turned the antibodies into a nasal spray. The idea is that these antibodies can neutralize any virus particles that enter the nose. A Phase 1 trial in Australia to test the safety and longevity of the antibodies is currently underway. How long the antibodies will last in the nose remains an open question, though. While the nose is a major entryway for the virus, it also regularly sweeps its passages of foreign material, washing it down into the gut with mucus.
Another team at the University of California, San Francisco is also taking the antibodies-in-the-nose approach, albeit with an aerosol spray containing antibodies inspired by a different animal. In August, they published a preprint describing a synthetic “nanobody” — an extra-tiny antibody found in llamas and camels — that interferes with the ability of the spike protein to interact with a key virus receptor known as ACE2 (short for angiotensin converting enzyme 2). The nanobody sticks directly to the part of the spike protein needed to interact with ACE2, thereby preventing it from getting into cells. There hasn’t been much news from the team since their August statement, but the San Francisco Public Press reported at the end of October that the team is hoping to test their aerosol, dubbed Aeronabs, as a nasal spray in early 2021 and begin production shortly thereafter.
Yet another team, associated with a Seattle-based biotech company called Neoleukin Therapeutics, is developing a nasal spray containing a decoy molecule also meant to block ACE2. In a paper published in Science on November 5, they described their method of developing over 35,000 potential decoy molecules and whittling down the list to the best one. The decoy bears a close resemblance to the SARS-CoV-2 spike protein, which normally latches onto the ACE2 enzyme when trying to get into a cell.
The idea is that the decoy can be sprayed into the nose, where it will stick to ACE2 receptors on cells, thereby preventing the coronavirus from getting its foot in the door. In early tests, hamsters that got the nasal spray were protected from Covid-19 infection, and a range of human cell lines that were treated with the decoy also avoided infection.
A few teams are taking a different approach by attempting to administer a vaccine, rather than an antiviral treatment, through the nose (quick refresher: a vaccine is meant to elicit a natural immune response from the body to attack the virus, not block the virus directly).
A team at Washington University in St. Louis is developing an intranasal vaccine for Covid-19 that’s based on a chimpanzee adenovirus, a type of cold virus (this is also the basis for AstraZeneca’s injected vaccine). In a paper published in Cell in August, the team shows that mice that received a single dose of their intranasal vaccine (in contrast, some injected vaccines require two doses) were fully protected from SARS-CoV-2. Notably, mice that were injected with the same vaccine had only partial protection. The team told Nature in September that administration through the nose “summoned potent ‘mucosal’ immune responses that can block the virus at the site of infection in the upper airways.”
In October, a team at the University of Houston announced a partnership with AuraVax Therapeutics to create an inhalable Covid-19 vaccine that uses the spike protein to elicit an antibody response. Its effectiveness is not yet known. A company called Altimmune, which partnered with the University of Alabama early in the pandemic, has a single-dose, intranasal vaccine candidate called AdCovid that it appears to be planning to manufacture at scale. On November 10, it announced an agreement with the biopharmaceutical manufacturing company Lonza to produce a vaccine (that is, if the clinical data support its advancement).