The SARS-CoV-2 virus has continued to evolve since the start of the pandemic, and we've moved down the list of variants before arriving at Omicron. Now, subvariants of Omicron are becoming dominant the world over. Scientists have said they really can't say what might come next. It seems likely that the virus will continue to evolve, potentially in a chronically ill patient. Another subvariant of Omicron may arise, but it's also possible that a new variant entirely may emerge, or a subvariant of something we've seen before, like Delta, may appear. If we are going to get ahead of the virus, we may have to develop a nasal spray, suggested new research in Science Immunology. An accompanying commentary stresses the importance of intranasal vaccines for COVID.
Previous work has shown that intranasal vaccines could be very effective, especially because that is how SARS-CoV-2 enters the body - through cells in the nasal and respiratory passages - the mucosal lining. Now, researchers have confirmed that by demonstrating that in the airways, the immune responses of people who have been vaccinated don't perform well compared to people who have been naturally infected with the virus. In the very place where the immune system should be ready to fight the virus, mRNA vaccines don't seem to be generating a robust response.
While mRNA vaccines are able to cause a general immune response, and have been effective at preventing serious illness in most people, there have been many breakthrough infections. This study helped explain why. It seems as though the immune response from mRNA vaccines stays mostly in the blood. So while antibodies are found in circulation that can fight the virus, cells that sit in the mucosal linings, where the virus is trying to cause an infection, only have a small or moderate neutralizing response.
Only unvaccinated people that had been very sick with COVID-19 attacked the virus in both the airways and the bloodstream, which the researchers noted is far from ideal.
"The Omicron variant almost completely escaped neutralization by mucosal antibodies in individuals who received mRNA vaccines and in previously infected individuals," said Jie Sun, a Professor of Medicine, among other appointments, at UVA. "Our data showed that mRNA vaccination also did not induce sufficient tissue-residing cellular immunity in the airways, another arm of our immune system to prevent the entry of the virus into our bodies."
The scientists also found a way forward, however. In a mouse model that was given an intranasal vaccine in combination with an mRNA vaccine, the immune response was vigorous in the bloodstream and in the lungs. These mice were able to attack both the original strain of SARS-CoV-2 as well as the Omicron variant, Sun said.
"Our data suggest that an intranasal vaccine-boosting strategy will be critical to protect people against emerging variants of concern," Sun noted. "The nasal vaccine provides a mucosal antigen boost to the pre-existing memory of T and B cells that direct immune response, resulting in higher cellular and humoral immunity."
Although there are intranasal vaccines in development for SARS-CoV-2/COVID-19, none have been approved for use in the US yet. Some that have already been made have shown the potential for side effects. An intranasal vaccine has been tested and approved in China, but the mucosal immunity it generates has not been evaluated yet, said Sun.
Sun's team was the first to demonstrate that the immune response to COVID-19 causes permanent lung damage in unvaccinated, hospitalized patients. They are planning to continue to study the virus and look for ways to stop it.