It’s clear that our current COVID-19 vaccines continue to be very effective at preventing hospitalization and death, even as the more transmissible Delta variant surges. But we now know they’re less good at thwarting the spread of the virus. And one reason could be where in the body the shots are delivered.
Vaccines that are injected into the arm, including the ones for COVID-19, do a great job of producing antibodies in the bloodstream. They don’t, however, generate high levels of antibodies in the nasal passages, which is where SARS-CoV-2, the coronavirus that causes COVID, is most likely to enter the body.
Of 469 people who were infected during the outbreak in Provincetown in July and studied by the Centers for Disease Control and Prevention, three-quarters were fully vaccinated. Overall, 274 of these vaccinated people were symptomatic. Five people needed to be hospitalized — four of whom were vaccinated — but none died. Genetic sequencing of virus samples revealed that 90 percent of the infected people had the Delta variant. Notably, vaccinated individuals carried as much virus in their noses as unvaccinated people did.
“We’re seeing this transmission issue because people are getting infected in the upper airway,” says Michael Diamond, a viral immunologist at Washington University in St. Louis, whose lab is working on a different kind of vaccine: one that’s sprayed in the nose. With the shot-in-the arm vaccination, Diamond says, “the virus is still able to replicate locally in the airway.”
That’s why he and other scientists believe that stopping the virus at its point of entry — the upper respiratory tract — could be a more effective strategy for halting its spread.
“We literally want to vaccinate the site of virus entry — the mucosal surface of the nose,” says Biao He, a professor of infectious diseases at the University of Georgia who also has a company, CyanVac, that is developing a nasal spray vaccine for COVID-19.
A nasal spray vaccine for flu already exists for children. Now nasal spray vaccines against SARS-CoV-2 are showing encouraging signs in mice, ferrets, hamsters, and monkeys. Human trials are just getting underway.
In July, California-based Meissa Vaccines began an early-stage trial to test its intranasal vaccine in 130 adults. It uses a live, weakened version of the coronavirus that can spur an immune response but can’t cause infection. CyanVac is beginning an initial trial of its nasal spray vaccine with 80 adults this month. It employs a harmless modified virus to shuttle the SARS-CoV-2 spike protein to cells. AstraZeneca, too, is working on an intranasal formulation of its viral vector vaccine, and eTheRNA Immunotherapies in Belgium is developing an mRNA-based one.
A challenge to advancing these vaccine trials is the need for healthy unvaccinated people: People who remain vaccine-hesitant are unlikely to sign up. One option is to test the vaccines in countries where other COVID-19 vaccines are not yet widely available. St. Louis-based Precision Virologics and Bharat Biotech, a vaccine manufacturer in India, have licensed Diamond’s technology and are conducting a nasal spray vaccine trial in India.
Fear of needles may be keeping some people from getting vaccinated. A survey by a group called Gavi, the Vaccine Alliance, found that needle phobia may be responsible for 10 percent of vaccine hesitancy. No syringes means intranasal vaccines could also be easier to give to children and cheaper to manufacture. Plus, they may not need to be administered by a health care professional.
While our current vaccines are no doubt marvels of science, we can’t rely on them to fully protect us against future coronavirus variants. We need more vaccines — and new ways to deliver them.