The Covid-19 vaccines approved for use today have been developed at unprecedented speed, exceeding expectations for their effectiveness. The billions of people they protect have avoided severe symptoms, hospitalizations and deaths. These vaccines are a scientific success beyond measure.
And yet they could be even better.
The enemy has evolved, and the world needs next-generation vaccines to respond. This includes vaccines that completely prevent infections with the coronavirus.
When the first mRNA vaccines were first approved in December 2020, the world was dealing with a different kind of pandemic. The dominant circulating strain had a relatively low ability to spread between humans. At that time, the mRNA vaccines offered not only strong protection against serious illness and death, but also high protection 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 able to bypass protective antibodies and cause widespread infections, despite ever-increasing immunity to vaccines and previous infections. Fortunately, after the booster, the mRNA vaccines are still very effective in preventing hospitalizations and deaths, even against the highly contagious Omicron variant.
So, one might ask, why should we worry about infection when we can eliminate much of the risk of serious illness and death through a combination of existing vaccines and treatments?
Even mild infections can develop into a long covid, with people suffering long-lasting, debilitating symptoms. The data also suggest that groups such as older adults who have been vaccinated but have not received their booster shot may remain at higher risk of the worst effects of Covid-19. Regular infections can significantly affect people’s lives, affect their ability to work and their children’s school attendance. There is also no guarantee that people infected with Omicron will remain protected from infections with future variants.
One change that could make vaccines more effective is that they can stop the virus as soon as it enters the body. This could contain both infections and the spread of the virus as a whole.
The currently available Covid-19 vaccines are injected into people’s arm muscles and are highly capable of fighting the virus once people are infected. But they’re not as successful at preventing people from getting infected in the first place. Ideally, you want to stop the spread of a virus exactly where people are infected: in the nasal cavity.
This is why groups of scientists, including myself, are working on nasal Covid vaccines. Ideally, a nasal vaccine could penetrate the lining of the mucus lining the nose and help the body make antibodies that capture the virus before it even has a chance to attach itself to people’s cells. This type of immunity is known as sterilizing immunity.
By catching viruses right at the site of infection, antibodies induced by nasal vaccines can give the body a head start in fighting the virus before it causes symptoms. Not only might nasal vaccines be better at preventing infection, but they can also develop the same type of immune system protection as other vaccines, and even stronger because that immune memory is at the portal of entry for the virus. These vaccines can create highly protective memory B cells, which produce faster and better antibodies against future infections, and memory T cells, which help kill infected cells and support the production of antibodies.
This type of vaccine has traditionally been considered more difficult to produce. The slime layer is a formidable barrier. Nor does the body generate a robust immune response simply by spraying a conventional vaccine up the nose. The approved nasal flu vaccine called FluMist uses weakened viruses to enter the cells of the nose and stimulate an immune system response. However, this approach is not safe for use in immunocompromised individuals.
The good news is that scientists like me believe we’ve found a way around this problem for SARS-CoV-2. We have shown in animal studies that by spraying the virus’s so-called spike proteins up the nose of a previously vaccinated host, we can significantly reduce infections in the nose and lungs and protect against illness and death. Combining this approach with ongoing efforts to develop a single vaccine for a broader spectrum of coronaviruses could also potentially offer people protection against future variants.
A big question is how long immunity to a nasal vaccine would last. So far, in animal experiments, antibodies and memory immune cells remain in the nose for months. Should that immunity wane over time, as with the other vaccines, using the nasal spray as a booster shot – possibly over the counter – every four to six months may make the most sense for this pandemic. This poses similar challenges to other boosters where uptake could be much higher, especially for high-risk groups. Encouraging people to get their boosters is crucial. But the barrier for a nasal spray booster can be lower than for a needle syringe for many people.
The world is in dire need of a vaccination strategy that puts immunological guards at the gates to prevent viral invaders from infecting us. There are several other approaches to nasal vaccines at different stages of clinical trials. And any success we are having in developing a nasal vaccine against Covid-19 will not be limited to this one virus. Nasal spray vaccination strategies can also be applied to other respiratory pathogens.
While there are still some obstacles, it is worth focusing on the potential immunological and health benefits of nasal spray vaccines now and in the years to come.