Gentle nasal spray vaccines against COVID, the flu and RSV are coming. They may work better than shots in the arm
lyson Velasquez hates needles. She never liked getting shots as a kid, and her anxiety only grew as she got older. “It really ballooned in my teens and early 20s,” she says. “It became a full-blown phobia.” She would panic at the sight of a needle being brought into an exam room; more than once she passed out. Velasquez says that she took an antianxiety medication before one appointment yet still ran around the room screaming inconsolably “like I was a small child; I was 22.
A few nasal vaccines have been introduced in the past, but they’ve been beset by problems. The flu inoculation FluMist has not gained popularity because of debates about its effectiveness, and a different vaccine was pulled from the market decades ago because some people had serious side effects. In China and India, nasal vaccines for COVID have been approved because those countries prioritized their development during the pandemic, whereas the U.S.
Intramuscular injection vaccines are good at preventing a disease from spreading, but they do not stop the initial infection. A nasal spray does a much better job. That’s because sprays are aimed directly at the spot where many viruses first enter the body: the nose and the tissue that lines it, called the mucosa.
It’s possible an inhaled vaccine may provide yet one more layer of protection, called trained innate immunity. This reaction is a bit of a mystery: although immunologists know it exists and appears also to be produced by intramuscular injections, they can’t quite explain how it works. Immune cells associated with trained innate immunity seem to have memorylike responses, reacting quickly against subsequent infections.
Jen Christiansen; Source: Florian Krammer, Icahn School of Medicine at Mount Sinai and Medical University of Vienna, Austria . “It’s naturally a respiratory pathogen,” so it infects nasal cells, says Michael Egan, CEO and chief scientific officer of CastleVax, a company that formed to develop the NDV vaccine for COVID. A small early clinical trial showed the CastleVax vaccine was safe and caused robust immune responses in people. “Those results were very promising,” Egan says.
Codagenix, which is developing CoviLiv, sidestepped the need for a new viral vector or an adjuvant by disabling a live SARS-CoV-2 virus. To make it safe, scientists engineered a version of the virus with 283 mutations, alterations to its genetic code that make it hard for the virus to replicate and harm the body. Without all these genetic changes, there would be a chance the virus could revert to a dangerous, pathogenic form.
Vaccines that don’t need to be injected could clear many barriers to vaccine access worldwide. “We saw with COVID there was no vaccine equity,” Smaill says. Many people in low-income countries never received a shot; they are still going without one four years after the vaccines debuted. Even high-income countries face barriers to vaccination, although they may be more personal than systemic. For very many people, the needle itself is the problem. Extreme phobia such as Velasquez’s is uncommon, but many people have a general fear of needles that makes vaccinations stressful or even impossible for them. For about one in 10 people needle-related fear or pain is a barrier to vaccinations, says C. Meghan McMurtry, a psychologist at the University of Guelph in Ontario.
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