The Covid-19 vaccines approved for use today were developed at an unprecedented speed, exceeding expectations in how well they worked. The billions of people they protect have avoided severe symptoms, hospitalization and deaths. These vaccines are an immeasurable scientific success.
And yet they could be even better.
The enemy has evolved and the world needs next-generation vaccines to respond. This includes vaccines that prevent coronavirus infections altogether.
When the early mRNA vaccines were first approved in December 2020, the world was dealing with a different kind of pandemic. The dominant species that circulated had a relatively low ability to spread between humans. At the time, the mRNA vaccines not only provided strong protection against serious illness and death, but they were also highly protective against infection and the spread of the virus.
But SARS-CoV-2 has continued to mutate, giving rise to variants that are more contagious and highly capable of evading protective antibodies, causing widespread infections, despite ever-increasing immunity to vaccines and previous infections. Fortunately, the mRNA vaccines after the booster injection are still very effective in preventing hospitalizations and deaths, including against the highly contagious Omicron variant.
So one might ask, if we can eliminate much of the serious risk of illness and death through a combination of existing vaccines and treatments, why should we worry about infections?
Even mild infections can develop into long-term Covid, with people experiencing long-lasting, debilitating symptoms. Data also suggests that groups such as older adults who have been vaccinated but have not received their boosters may be at higher risk for the worst outcomes of Covid-19. Regular infections can significantly disrupt people’s lives, affecting their ability to work and keep their children in school. There is also no guarantee that people infected with Omicron will remain protected from infection with future variants.
One change that could make vaccines more effective is if they can stop the virus right as it enters the body. This could reduce the number of infections and the spread of the virus.
The currently available Covid-19 vaccines are injected into people’s arm muscles and are very capable of fighting the virus once people are infected. But they aren’t as successful at keeping people from getting infected to begin with. To do that, you ideally want to prevent a virus from spreading in the place where people become infected: the nasal cavity.
For this reason, groups of scientists, including myself, are working on nasal Covid vaccines. Ideally, a nasal vaccine could penetrate the mucus lining in the nose and help the body make antibodies that trap the virus before it even has a chance to attach to people’s cells. This type of immunity is known as sterilizing immunity.
By trapping viruses directly at the site of infection, nasal vaccine-induced antibodies can give the body a head start in fighting the virus before it causes symptoms. Nasal vaccines could not only be better positioned to prevent infections, but they could also develop the same kind of immune system protection as other vaccines, and even stronger because this immune memory is the gateway to virus entry. These vaccines can form highly protective memory B cells, which make faster and better antibodies against future infections, and memory T cells, which help kill infected cells and support antibody production.
These types of vaccines have traditionally been considered more difficult to make. The slime layer is a formidable barrier. The body also does not generate a robust immune response by simply injecting a conventional vaccine into the nose. The approved nasal flu vaccine, called FluMist, uses weakened viruses to get into the cells in the nose and stimulate an immune system response. But this approach is not safe for use in immunocompromised people.
The good news is that scientists like me think we’ve found a way around this problem for SARS-CoV-2. We have shown in animal studies that we can inject the virus’s so-called spike proteins into the nose of a previously vaccinated host and significantly reduce infection in the nose and lungs and provide protection against illness and death. Combining this approach with efforts underway to develop a single vaccine for a wider range of coronaviruses could potentially protect people from future variants as well.
A big question is how long the immunity from a nasal vaccine would last. So far, in animal studies, antibodies and memory immune cells remain in the nose for months. Should this immunity wane over time, as with the other vaccines, using the nasal spray as a booster — potentially over-the-counter — every four to six months may make the most sense for this pandemic. This presents similar challenges to other boosters, where uptake could be much higher, especially for high-risk groups. Encouraging people to get their boosters is critical. But the barrier for a nasal spray booster may be lower for many people than for a needle injection.
The world desperately needs a vaccine strategy that puts immune guards outside its gates to prevent viral invaders from infecting us. There are several other nasal vaccine approaches in various phases of clinical trials. And all the success we have in developing a nasal vaccine for Covid-19 will not be limited to this one virus. Nasal spray vaccine strategies can also be applied to other respiratory pathogens.
While there are still some hurdles, the potential immunological and public health benefits of nasal spray vaccines are worth focusing on now and for years to come.
Akiko Iwasaki (@VirusesImmunity) is a professor of immunobiology at the Yale School of Medicine and an investigator at the Howard Hughes Medical Institute. She is also a co-founder of Xanadu Bio, a start-up that hopes to produce and test a nasal spray vaccine.
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