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Inhalation-based vaccinations shown to provide long-lasting protection against SARS-CoV-2

The inhalation-based vaccine showed to be equally as effective as currently used COVID-19 vaccinations, at fractions of the current dose.

Researchers from McMaster University have demonstrated that an inhalation-based COVID-19 vaccine can give wide, long-lasting protection against the original SARS-CoV-2 strain and variations of concern.

The study, which was published in the journal Cell on February 9th, uncovers the immunological processes and major advantages of vaccinations administered directly into the respiratory system rather than through intramuscular injection.

According to the researchers, inhaled vaccinations are significantly more effective in generating an immune response because they target the lungs and upper airways, where respiratory viruses initially enter the body.

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

Michael D’Agostino demonstrates how to use the inhalation-based vaccine. (Credit: Georgia Kirkos/Mcmaster University)

The vaccination technique used in the study was based on a different program investigating the tuberculosis vaccine, which was started by Zhou Xing, a co-lead author of the paper.

“What we’ve 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,” Xing says.

Co-lead author added his thoughts, stating, “”We wanted, first and foremost, to design a vaccine that would work well against any variant….Current vaccines are limited because they will need to be updated and will always be chasing the virus.”

The researchers developed two different vaccines, both being adenovirus-based. Because they are intended to target three components of the virus, including two that are highly conserved across coronaviruses and do not evolve as fast as spike, both forms of the new McMaster vaccine are effective against highly transmissible strains.

All COVID vaccines licensed in Canada so far solely target the spike protein, which has demonstrated a remarkable propensity to mutate.

“We have revealed in our report that besides neutralizing antibodies and T cell immunity, the vaccine delivered into the lungs stimulates a unique form of immunity known as trained innate immunity, which is able to provide very broad protection against many lung pathogens besides SARS-CoV-2,” Xing said.

The team showed that their 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 existing vaccinations — perhaps as low as 1% — meaning a single batch of vaccine might travel 100 times farther.

The researchers suggest that being able to show that this new delivery technique can greatly increase vaccine supplies, especially in a pandemic situation, might be a game changer.


The study was published in Cell on February 9th, 2022.

Abstract. The emerging SARS-CoV-2 variants of concern (VOC) threaten the effectiveness of current COVID-19 vaccines administered intramuscularly and designed to only target the spike protein. There is a pressing need to develop next-generation vaccine strategies for broader and long-lasting protection. Using adenoviral vectors (Ad) of human and chimpanzee origin, we evaluated Ad-vectored trivalent COVID-19 vaccines expressing Spike-1, Nucleocapsid and RdRp antigens in murine models. We show that single-dose intranasal immunization, particularly with chimpanzee Ad-vectored vaccine, is superior to intramuscular immunization in induction of the tripartite protective immunity consisting of local and systemic antibody responses, mucosal tissue-resident memory T cells and mucosal trained innate immunity. We further show that intranasal immunization provides protection against both the ancestral SARS-CoV-2 and two VOC, B.1.1.7 and B.1.351. Our findings indicate that respiratory mucosal delivery of Ad-vectored multivalent vaccine represents an effective next-generation COVID-19 vaccine strategy to induce all-around mucosal immunity against current and future VOC.

Afkhami, S., D’Agostino, M., Xing, Z. et al. 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

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