Recently designed inhaled vaccination provides extensive protection against SARS-CoV-2 and related variants.

Scientists from McMaster University have proven that an inhaled version of the COVID vaccine can provide wide, long-lasting protection against the original SARS-CoV-2 strain and variations of concern.

The study, which was published in the journal Cell recently, exposes the immunological mechanisms and major benefits of vaccines administered directly into the respiratory system rather than by injection.

Inhaled vaccines are significantly more successful at triggering a protective immune response because they target the lungs and upper airways, where respiratory viruses initially enter the body, according to the researchers.

The described preclinical investigation, which was conducted on animal models, provided the necessary proof of concept that enabled a Phase 1 clinical trial to evaluate inhaled aerosol vaccines in healthy humans who had already received two doses of a COVID mRNA vaccine, which is presently underway.

The tested COVID vaccine technique was based on Zhou Xing, a co-lead author of the current study and a professor at the McMaster Immunology Development Centre and Department of Medicine, who constructed a comprehensive tuberculosis vaccine research programme.

"What we've discovered after years of research is that the vaccine delivered into the lung promotes all-around protective respiratory mucosal immunity, which the injected vaccine lacks," adds Xing.

COVID vaccinations that are now approved are all injected.

"First and foremost," says Matthew Miller, an associate professor at McMaster's Michael G. DeGroote Institute for Infectious Disease Research, "we sought to build a vaccine that would perform well against any variation."

Only a few COVID vaccines have been developed in Canada, and McMaster's is one of them. The urgent effort is a crucial mission of Canada's Global Nexus for Pandemics and Biological Threats, which is housed at McMaster.

For the vaccine, researchers evaluated two types of adenovirus platforms. The viruses act as vectors, allowing vaccine to be delivered directly to the lungs without causing disease.

"With our vaccine strategy, we can stay ahead of the infection," Miller says. "Right now, vaccines are limited since they must be updated and are continually chasing the virus."

Because they are designed to target three components of the virus, including two that are highly conserved among coronaviruses and do not evolve as quickly as spike, both forms of the new McMaster vaccine are effective against highly transmissible versions. All COVID vaccines licenced in Canada so far solely target the spike protein, which has demonstrated a remarkable propensity to mutate.

"This vaccine may also provide pre-emptive protection against a future pandemic, which is critical because, as we've seen during this pandemic — and as we saw in 2009 with the swine flu — even if we can quickly develop a pandemic virus vaccine, it's already too late. Despite the fact that we were able to develop a vaccine in record speed, millions of people died "Miller explains.

"We revealed in our report that, in addition to neutralising antibodies and T cell immunity, the vaccine delivered into the lungs stimulates a unique type of immunity known as trained innate immunity, which can provide very broad protection against a variety of lung pathogens other than SARS-CoV-2," Xing adds.

An inhaled vaccine is so effective at targeting the lungs and upper airways that it can offer optimum protection with a fraction of the dose of current vaccines — possibly as little as 1% — meaning a single batch of vaccine might travel 100 times further, according to the researchers.

Reference:

Sam Afkhami, Michael R. D’Agostino, Ali Zhang, Hannah D. Stacey, Art Marzok, Alisha Kang, Ramandeep Singh, Jegarubee Bavananthasivam, Gluke Ye, Xiangqian Luo, Fuan Wang, Jann C. Ang, Anna Zganiacz, Uma Sankar, Natallia Kazhdan, Joshua F.E. Koenig, Allyssa Phelps, Steven F. Gameiro, Shangguo Tang, Manel Jordana, Yonghong Wan, Karen L. Mossman, Mangalakumari Jeyanathan, Amy Gillgrass, Maria Fe C. Medina, Fiona Smaill, Brian D. Lichty, Matthew S. Miller, Zhou Xing. Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2. Cell, 2022; DOI: 10.1016/j.cell.2022.02.005