TThe colossal success of Covid vaccines – in countries with access to them – has resulted in deaths and severe illness from infection even as the virus has evolved to outpace immunity and shred the population more quickly.
But while the rapid development of Covid shots ranks as the pandemic’s best achievement, scientists are far from done. In a small number of laboratories around the world, teams are dealing with a problem that cannot be ignored: that the virus remains rampant in the face of herd immunity.
The problem arose because the existing Covid vaccines are better at preparing the immune system to fight the virus inside the body than stopping it at the gates. So, even though immunity has largely tarnished Covid, countries still face waves of infections that transport vulnerable people to hospitals, keep employees out of work, and leave an uncertain proportion of people infected with Covid for an extended period.
Hopes of stopping the spread of infection rest on the development of vaccines that are given as a nasal spray rather than an injection into the arm. It aims to produce strong immune protection in the nose and throat, where most Covid infections gain a foothold. In addition to their ability to prevent infection, nasal sprays may be more acceptable to people who are not interested in needles.
“If you think of your body as a fortress, intramuscular grafting really protects the interior of your castle, so once invaders are in, that immunity protects them from taking the throne,” said Dr. Shaun Liu, medical director of the Covid Clinical Center. The Experiments Unit at the Icahn School of Medicine at Mount Sinai in New York City.
“But if you train your immune system to work at the castle gates, not only will invaders have a hard time getting in, they may have a hard time spreading inside.”
Liu is conducting an early trial of an intranasal Covid vaccine made in a similar way to seasonal flu vaccines, meaning it could be produced by the same facilities and dramatically improve global access to Covid vaccines.
More than a dozen clinical trials of intranasal Covid vaccines are underway, but the process is not without its challenges. For the vaccine to work inside the nose, it must produce a strong and permanent immune response in the nasal mucosa, the moist membrane that lines the inside of the nose. It also helps if people don’t swallow or sneeze, which can make reliable dosing difficult.
The widely used Pfizer and Moderna vaccines are not immediately suitable for intranasal delivery. Both vaccines use tiny lipid nanoparticles to smuggle the genetic instructions (RNA) for the coronavirus protein into cells that activate the immune system.
“Theoretically, RNA vaccines could work, but no one has figured out how to deliver them as an effective intranasal spray,” said Professor Robin Shattuck, Head of Mucosal Infection and Immunology at Imperial College London.
“Lipid nanoparticles are very sensitive and work beautifully when injected into the body, but it’s a bigger engineering problem to figure out how to get them into the nose, transport them through the mucus, and into the cells.”
So far, only one intranasal vaccine has found a wide market, the AstraZeneca influenza spray, which is marketed as Flumist in the United States and – given possible misunderstandings in Germany – Flumist in Europe. The vaccine uses a weakened influenza virus, which can reach the cells of the lining of the nose and provoke an immune reaction. It not only protects the individual from influenza, but helps reduce societal infection, an achievement scientists want to replicate with Covid.
Results from an early trial of a nasal version of the Oxford/AstraZeneca vaccine are expected to be published soon. The Oxford vaccine is based on a weakened adenovirus, which may be able to induce an immune response in the nose. But all researchers face hurdles with nasal vaccines, including measuring the strength of the immune response, knowing how protective it is, and how long it lasts. If the nasal vaccine provides strong protection against infection, but only for a few months, it may work better as a fall booster, with the addition of the Covid vaccines providing more permanent “systemic” protection against severe disease.
“I think you want the systemic vaccine as well because it’s very important to protect against severe disease,” said Professor Peter Openshaw, a member of the government’s Advisory Group on New and Emerging Respiratory Virus Threats (Nerftag). “I don’t want to rely solely on a purely mucosal immunization unless it is also able to generate a decent systemic response.”
Dr Sandy Douglas, a pharmacist working on the Oxford vaccine, does not expect any intranasal Covid vaccines to be available this year. “No one should put off getting their intramuscular vaccine to wait for the nasal spray,” he said.
“But as a mid-term horizon, this is one of the most important questions in vaccinology, not just for Covid, but for the next pandemic,” he added. How do we make good vaccines to stop respiratory viruses completely? We need to solve this problem as soon as possible. It might take quite a bit of effort and investment, but I’d say it’s totally worth it. We can see how big the advantage would be if we had vaccines that stopped infection completely. “