The jealous success of Covid vaccines – in countries that can get them – has led to deaths and severe infections that are declining sharply, even as the virus evolves to bypass immunity and tear populations faster.
But while the rapid development of Covid’s photos ranks as the best achievement of the pandemic, scientists are still not done. In a small number of laboratories around the world, teams are tackling a problem that cannot be ignored: that the virus continues to spread in the face of mass immunity.
The problem arose because existing Covid vaccines are better at preparing the immune system to fight the virus inside the body than stopping it at the gates. So, although immunity has largely “discolored” Covid, countries are still facing waves of infections that hospitalize vulnerable people, prevent employees from working and leave insecure people with long-term Covid.
Hopes to stop the spread of the infection are based on the development of vaccines that are delivered by nasal spray rather than by shot in the arm. They aim to create a strong immune defense in the nose and throat, where most Covid infections are established. Beyond their potential to block infections, intranasal sprays may be more acceptable for people who don’t like needles.
“If you think of your body as a castle, intramuscular vaccination really protects the interior of your castle, so once invaders come in, that immunity protects them from taking the throne,” said Dr Sean Liu, medical director of the Covid Clinical Clinic. . testing department at Icahn Medical School in Mount Sinai, New York.
“But if you train your immune system to work at the castle gates, then the invaders will not only have trouble entering, but may have trouble spreading inside.”
Liu is conducting an early-stage trial of an intranasal Covid vaccine made in a similar way to seasonal flu vaccines, which means it can be produced from 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 challenges. For the intranasal vaccine to work, it must elicit a strong and long-lasting immune response in the nasal mucosa, the moist membrane that covers the inside of the nose. It also helps if people do not swallow or sneeze, which can make reliable dosing difficult.
The widely used Pfizer and Moderna vaccines do not respond immediately to intranasal delivery. Both vaccines use small, fatty nanoparticles to transfer the genetic instructions (RNA) for the coronavirus protein into the cells that prepare the immune system.
“In theory, RNA vaccines could work, but no one has developed how to deliver them as an effective intranasal spray,” said Prof. Robin Shatok, head of the Department of Mucosal Infections and Immunity at Imperial College London.
“Lipid nanoparticles are quite delicate and work great when you inject them into the body, but it’s more of an engineering problem to understand how to deliver them to the nose, transfer them through mucus and cells.”
So far, only one intranasal vaccine has found a wide market, namely the AstraZeneca flu spray sold as Flumist in the US and – given potential misunderstandings in Germany – Fluenz in Europe. The vaccine uses a weakened influenza virus that can penetrate the cells of the nasal mucosa and provoke an immune response. It not only protects the individual from the flu, but helps reduce infections in the community, a feat that scientists want to replicate with Covid.
A recent study of an intranasal version of the Oxford / AstraZeneca vaccine is expected to publish results. The Oxford vaccine is based on a weakened adenovirus that may be able to elicit an immune response in the nose. But all researchers are faced with obstacles to intranasal vaccines, including measuring the strength of the immune response, knowing how protective it will be and how long it can last. If the intranasal vaccine provides strong protection against infection, but only for a few months, it may work best as an autumn booster, supplementing Covid injections, which provide more lasting “systemic” protection against severe disease.
“I think you would also like a systemic vaccine because it is so important in protecting against serious diseases,” said Prof. Peter Openshaw, a member of the government’s Advisory Group on New and Emerging Respiratory Viral Threats (Nervtag). “I wouldn’t want to rely solely on mucosal immunization unless it can generate a decent systemic response.”
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Dr. Sandy Douglas, a pharmacist working on the vaccine in Oxford, does not expect to have intranasal vaccines against Covid this year. “No one has to delay their intramuscular vaccine to wait for a nasal spray,” he said.
“But as a medium-term perspective, this is one of the most important issues in vaccinology, not only for Covid, but for the next pandemic,” he added. “How do we make vaccines that are good for stopping respiratory virus infections?” We need to resolve this issue as soon as possible. It may be necessary to make significant efforts and investments, but I would say that it is absolutely worth it. We can see how great the advantage would be if we had vaccines that completely stop the infection. “
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