An inhaled form of COVID-19 vaccine developed by scientists at McMaster University in Canada can provide broad, long-lasting protection against the SARS-CoV-2 variants of concern, a preclinical study has found. The research, published recently in the journal Cell, shows the immune mechanisms and significant benefits of vaccines being delivered directly into the respiratory tract, rather than by traditional injection.
Because inhaled vaccines target the lungs and upper airways where respiratory viruses first enter the body, they are far more effective at inducing a protective immune response, the researchers said. The study, which was conducted on animal models, has provided the critical proof of concept to enable a Phase 1 clinical trial that is currently under way to evaluate inhaled aerosol vaccines in healthy adults who had already received two doses of a COVID-19 mRNA vaccine.
The strategy was built upon a robust tuberculosis vaccine research programme established by Zhou Xing, a co-lead author of the study. "What we have discovered from many years' research is that the vaccine delivered into the lung induces all-around protective respiratory mucosal immunity, a property that the injected vaccine is lacking," said Xing, professor at McMaster University.
"We wanted, first and foremost, to design a vaccine that would work well against any variant," added the study's co-lead author Matthew Miller, an associate professor at McMaster. Researchers compared two types of adenovirus platforms for the vaccine. The adenoviruses serve as vectors that can deliver vaccine directly to the lungs without causing illness themselves.
"We can remain ahead of the virus with our vaccine strategy. Current vaccines are limited because they will need to be updated and will always be chasing the virus," said Miller. Both types of the new vaccine are effective against highly transmissible variants because they are designed to target three parts of the virus, including two that are highly conserved among coronaviruses and do not mutate as quickly as spike, the researchers said.
All COVID-19 vaccines currently approved target only the spike protein, which has shown a remarkable ability to mutate, they said. The SARS-CoV-2 virus uses the spike protein to enter and infect the human cells. "This vaccine might also provide pre-emptive protection against a future pandemic, and that is really important because as we have seen during this pandemic — and as we saw in 2009 with the swine flu — even when we are able to rapidly make a vaccine for a pandemic virus, it's already way too late," said Miller.
"Millions of people died, even though we were able to make a vaccine in record time," he said. The researchers found that besides neutralising antibodies and T cell immunity, the vaccine delivered into the lungs stimulates a unique form of immunity known as trained innate immunity.
This type of immunity is able to provide very broad protection against many lung pathogens besides SARS-CoV-2, they said. In addition to being needle and pain-free, an inhaled vaccine is so efficient at targeting the lungs and upper airways that it can achieve maximum protection, the researchers said.
This protection can be achieved with a small fraction of the dose of current vaccines — possibly as little as 1 per cent — meaning a single batch of vaccine could go 100 times further, they said. "This pandemic has shown us that vaccine supply can be a huge challenge," said associate professor Brian Lichty, who co-led the preclinical study.
"Demonstrating that this alternative delivery method can significantly extend vaccine supply could be a game changer, particularly in a pandemic setting," Lichty added.
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