A team led by CITF-funded researcher Dr. Jun Liu at the University of Toronto have demonstrated that a novel intranasal COVID-19 vaccine product can induce robust mucosal and systemic immune responses in a mouse model of SARS-CoV-2 infection. This is significant because existing vaccines, which are highly effective at inducing antibodies systemically (in the bloodstream), may not be as effective in inducing antibodies in mucosal tissues, such as the upper respiratory tract, which is the site of attack for respiratory pathogens like SARS-CoV-2. By directly inducing protective immunity at the potential site of infection, intranasal vaccines may be more effective in preventing breakthrough infections. The results are published in Cell Biosciences.

Key points:

  • The researchers developed a vaccine using a third-generation helper-dependent adenoviral vector (HD-Ad) platform with a SARS-CoV-2 receptor-binding domain (RBD) insert.
  • They utilized a transgenic mouse model transfected with human ACE2 receptors to evaluate the efficacy of this vaccine and demonstrated that intranasal administration of this vaccine resulted in complete protection of the upper and lower respiratory tract against SARS-CoV-2 infection, as well as prevention of inflammation in mouse lungs.
  • They state that the platform does not generate unwanted adenoviral proteins, but does generate high levels of the RBD protein to prime the immune system against the RBD portion of the spike protein of SARS-CoV-2.
  • The authors identified that a two-dose regimen of the intranasal vaccine spaced 21 days apart induced robust systemic and mucosal anti-RBD IgG and IgA antibody responses, and robust cell-mediated immunity (anti-RBD IFNg+ CD4+ T cells) in the lungs.

This study demonstrates the potential for an intranasal vaccine platform that could be effective in inducing protection against SARS-CoV-2 at the mucosal surfaces (upper and lower respiratory tracts). Another advantage of an intranasal vaccine is that it does not require an injection, offering a appealing alternative for people who might suffer from hesitancy related to a fear of needles.

Cao H, Mai J, Zhou Z, Li Z, Duan R, Watt J, Chen Z, Bandara RA, Li M, Ahn SK, Poon B, Christie-Holmes N, Gray-Owen SD, Banerjee A, Mossman K, Kozak R, Mubareka S, Rini JM, Hu J, Liu J. Intranasal HD-Ad vaccine protects the upper and lower respiratory tracts of hACE2 mice against SARS-CoV-2. Cell Biosci. 2021 Dec 8;11(1):202. doi: 10.1186/s13578-021-00723-0. PMID: 34879865; PMCID: PMC8653804.