Intranasal vaccines for COVID-19 will be critical to protect people against the emerging variants of concern of the SARS-CoV-2 virus, according to a study. Researchers at the University of Virginia (UVA) in the US noted that the widely available COVID-19 vaccinations keeping the majority of the population free from serious illness will not be enough to stop the spread of the virus and its variants.
The study, published recently in the journal Science Immunology, documents for the first time the underperforming immune response in the airways of people with COVID-19 vaccinations compared to those with natural infection. “Our data suggest that an intranasal vaccine-boosting strategy will be critical to protect people against emerging variants of concern,” said Jie Sun, a professor at UVA.
The mRNA vaccines such as Pfizer and Moderna take inspiration from messenger ribonucleic acid, the delivery system that facilitates biological reproduction. However, the mRNA in the vaccines is not derived from a live virus. Instead, the molecule is synthesised in a lab to resemble an invader, enough so that the body can recognise the real thing in the future.
The researchers noted that with these vaccines, “the message” now appears to be largely confined to the blood. The study found that bloodstreams get strongly ramped up by the vaccine, while the mucosal linings — moist, inner lining of some organs — experience moderate or little neutralising antibody response.
“The Omicron variant almost completely escaped neutralisation by mucosal antibodies in individuals who received mRNA vaccines and in previously infected individuals,” said Sun. “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,” he added.
The researchers found that only the bodies of unvaccinated patients who were seriously ill put up a vigorous fight against the virus in both their airways and their bloodstreams. However, the new study provides hope that vaccinations will one day soon provide complete coverage, the researchers said.
Mice that were administered a nasally delivered vaccine originating from adenovirus, a relative in the family of cold viruses that expresses the spike protein found in COVID-19, demonstrated “robust neutralising antibody responses” in combination with mRNA vaccine shots, they said. The SARS-CoV-2 virus uses the spike protein to enter and infect the human cells.
“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,” Sun explained. The uptick was found not only in the bronchi of the lungs, but also as an improvement over the bloodstream’s normal vaccinated response.
The immune response was “effective against the ancestral virus as well as the Omicron variant,” he said. The study also validates scientists’ suspicion that greater immunity to the coronavirus can be developed starting where the virus first takes root, the mucus membranes of the nose.
“We think the robust antibody responses in the respiratory tract (in humans) would neutralise the virus immediately upon viral entry when the individual contracts the virus, preventing the establishment of viral infection and subsequent passing of the infection to others,” Sun said. Pharmaceutical labs are working on COVID-19 nasal vaccines, but to date, none has been approved for use.
A spray would require a weakened version of the live virus. If the live virus is too weak, the spray won’t work. If it’s too strong, people will get sick and the virus will spread, according to the researchers. An adenovirus-based nasal vaccine has also yet to be approved for humans, mainly out of a fear of unwanted side effects. One of them could be Bell’s palsy, a condition that causes muscle weakness in the face, they said.
A study found a possible connection after people were vaccinated with an influenza nasal vaccine specially formulated to create a stronger immune response, the researchers said. “For a nasal vaccine, we do need to be more careful about the safety profiles,” Sun said.
“So I think we need a step-up trial from a mouse to human study in the US. A human trial has been performed in China already using nasal adenovirus spray, which suggests it is generally safe and can boost good immune responses, but mucosal immunity was not examined,” Sun added.