Nasal Delivery of Highly Effective COVID-19 Vaccines using Helper-Dependent Adenoviral Vectors


The pursuit of a safe and efficacious vaccine against SARS-CoV-2 has been the focus of efforts aimed at ending the COVID-19 global pandemic.  Many platforms have been investigated including RNA and DNA, virus-like particles and viral vectors, recombinant proteins, and both live attenuated and inactivated viruses.  Of these, the RNA vaccines have been among the first to market, largely due to a reduced development and production time.  However, vaccines that eliminate the possibility of transmission, provide longer lasting immunity, increase protection in specific populations (such as the elderly, children, pregnant women or immunocompromised patients) and employ simpler and more efficacious modes of administration (e.g. nasal delivery), may prove to be key in controlling COVID-19 and its emerging variants in the long term.



Inventors at the University of Toronto and the Hospital for Sick Children have developed a helper-dependent adenoviral (HD-Ad) vector-based vaccine for SARS-COV-2.  HD-Ad vectors are based on adenoviral (Ad) vectors, but they are completely devoid of adenoviral coding sequences. They are consequently safer than vaccines based on conventional Ad vectors.  Moreover, the SARS-CoV-2 antigens used in these HD-Ad vectors incorporate unique features aimed at presenting the S-protein in a context like that found in the natural virus.  Finally, intranasal delivery allows for protection of both the upper and lower airways (Figure 1) which is expected to reduce transmission compared to current generation vaccines.

Figure 1.  Current COVID-19 vaccines are administered intramuscularly and largely result in protection of only the lower respiratory tract.  Intranasal delivery is easily administered and leads to protection of both the upper and lower respiratory tracts, an outcome expected to reduce viral transmission between individuals.



  • Non-invasive aerosol delivery through inhalation
  • Protection of the upper airways reduces transmission of the virus after vaccination
  • Robust mucosal immunity in addition to systemic immunity
    • Intranasal delivery of two doses of the vaccine (5x109 vaccine particles, prime and boost, three weeks apart) generated high levels of antigen-specific IgG (titer: 106) and neutralizing antibody (titer: 103), as well as robust antigen-specific-T cell responses (IFN-g or TNF secretion) in immunized BALB/c mice.
    • A single dose elicited strong immune responses for at least six months indicating the potential for long-term protection
  • Multivalent vaccine development is facilitated by the large DNA coding capacity of HD-Ad vectors



  • Vaccine for SARS-COV-2



  • Provisional patent filed



Two vaccines have been found to elicit strong mucosal and systemic immune responses in BALB/c mice. One of them has been tested in K18-hACE2 mice via nasal delivery and in viral challenge experiments it provided full protection from SARS-CoV-2 infection in the upper (oropharyngeal swabs) and lower respiratory tracts (lungs).  These immune responses and protection effects are superior to that of the COVID-19 vaccines currently approved.  HD-Ad based multivalent vaccines targeting new variants of SARS-CoV-2 are currently being tested.




Virus , Covid-19 , SARS-COV-2 , vaccine , mRNA , adenovirus

VPRI Contact

Jae-Ho Yoo

Innovations and Entrepreneurship Manager
Innovations & Partnerships Office (IPO)

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