Inhaled aerosol COVID-19 vaccine safe and may boost mucosal immunity in the airways

Results from a phase 1 study of an inhaled COVID-19 vaccine suggest it is safe for human use and may provide an extra layer of protection against infection.The vaccine is inhaled as an aerosol mist. This novel delivery method means the vaccine is carried directly into the lungs. The thought is that it could enhance the immune response in the mucosal layers of the respiratory tract. Previous research suggests this is a gap in the immune strategy provided by current vaccines.“Even though they have significantly reduced incidence of death and hospitalization, the current COVID-19 vaccines have generally not provided protection against breakthrough infections,” said Dr. Fiona Smaill, a co-author of the study and professor emerita in the department of pathology and molecular medicine at McMaster University. “Our studies suggest that this is in part due to their inability to provide strong mucosal immunity in the lower respiratory tract—something our inhaled vaccine does quite well. This trial has made a strong case for inhaled vaccines to become a key tool in the prevention of future outbreaks and pandemics.”The 36 adult participants in the phase 1 trial were all previously vaccinated with at least two doses of injected COVID-19 mRNA vaccine. Nine had contracted COVID-19 in the past and 27 had no history of COVID-19. Participants were given one dose of vaccine and followed for 48 weeks. Researchers investigated four dosage strengths, with at least three participants getting each dosage strength. The inhaled vaccine expresses both SARS-CoV-2 spike antigens and also internal viral antigens. It uses either a human adenoviral vector or chimpanzee adenoviral vector. Researchers at McMaster University in Hamilton, Ont. carried out the trial from 2022 to 2024. All doses of the vaccine were well tolerated. The most commonly reported adverse events were mild fatigue, headache and cough. There were no changes in respiratory function after 12 weeks.The findings suggest that the inhaled vaccine provided participants with three layers of mucosal defence in the respiratory tract. Baseline data from the participants, both those who had a history of COVID-19 and those who had no infection history, showed minimal mucosal immunity to SARS-CoV-2 in the mucosal layer of the lungs, but the vaccine may have improved immunity in three ways. First, it increased the overall T-cell responses in the airways in a dose-dependent manner. T-cell responses to SARS-CoV-2 are thought to be more conserved across SARS-CoV-2 variants than antibodies that bind to spike protein antigens, the researchers wrote. Second and third, the phase 1 trial results indicate that the vaccine also improved trained innate immunity and antibody immunity in the respiratory mucosa.The chimpanzee adenoviral-vectored vaccine provided better results in immunogenicity than the human adenoviral-vectored vaccine.Results from the phase 1 trial also indicate that the vaccine also produced a systemic immune response.A phase 2 trial is currently in progress, with participants enrolled in three sites: McMaster University in Hamilton, Ont., The Ottawa Hospital Research Institute, and the Canadian Centre for Vaccinology at Dalhousie University in Halifax. The trial will involve 350 participants who have already been vaccinated with at least three doses of a COVID-19 mRNA vaccine. Researchers will randomize participants to receive either the inhaled vaccine or placebo. The Canadian Institutes for Health Research is funding the trial. Other inhaled COVID-19 vaccine candidates use an intranasal delivery, but recent studies suggest inhaled aerosol delivery may provide a better response. Only 11 of 160 COVID-19 vaccine candidates in clinical development involve inhaled delivery, and most use intranasal, the researchers report. The results of the phase 1 trial were published in Nature Communications.

Inhaled aerosol COVID-19 vaccine safe and may boost mucosal immunity in the airways

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