Intranasal administration of protein vaccines shows potential for protection against SARS-CoV-2 infection

In a CITF-funded study published in Vaccines, Dr. Marc-André Langlois (University of Ottawa) found that adjuvanted protein vaccinesMore precisely, the vaccine under study is composed of a SARS-CoV-2 spike protein or its receptor binding domain (RBD), combined with either cholera toxin (CT) or an archaeal lipid mucosal adjuvant (AMVAD) to elicit superior and long-lasting immune responses. administered intranasally can elicit strong both systemic and mucosal antibody responses against SARS-CoV-2 variants in mice. Though studies in humans are needed to guide the design of potential new intranasal vaccines, they hold potential to stave off SARS-CoV-2 infection. These vaccines were formulated as part of this research and are not yet being developed.

Currently approved vaccines are effective in inducing robust systemic immunity that protects against severe disease and death, but they do not protect against infection in the upper respiratory tract, the primary entry point for SARS-CoV-2. In addition, the continuous evolution of SARS-CoV-2 strains has resulted in variants capable of immune evasion and increased transmissibility. New vaccines involving mucosal immunity may, therefore, provide a solution to overcome these challenges.

Key findings:

• Two doses of adjuvanted protein vaccinesThe adjuvanted protein vaccines are composed of either a spike protein or its receptor binding domain (RBD), combined with an adjuvant chosen between cholera toxin (CT) and an archaeal lipid mucosal adjuvant (AMVAD). resulted in significant levels of immunoglobulin (Ig) GIgG is the most common type of antibody, found in the blood serum and other body fluids antibodies in plasma (indicating systemic immunity) and IgA antibodiesIgA are antibodies found in mucous membranes, mainly in the respiratory and digestive tracts. in fluids from the nose, bronchi and lungs (indicating mucosal immunity). The two adjuvantsCholera toxin (CT) and the archaeal lipid mucosal adjuvant (AMVAD). slightly differed in their effectiveness in inducing systemic or mucosal responses.
• The adjuvanted protein vaccines elicited mucosal and systemic neutralizing responses. The systemic antibody response observed in mice had a comparable neutralization capacity to that elicited in humans by a SARS-CoV-2 infection or two mRNA vaccine doses.
• The vaccine based on an adjuvanted spike protein led to higher mucosal IgA responses than the one based on the adjuvanted RBD antigen.
• The spike-based vaccine resulted in neutralizing plasma antibodies broadly targeting the wild type or ancestral, Delta and Omicron variants, whereas the RBD-based vaccine elicited a narrower antibody response with neutralizing activity only against the wild type and Delta variants.

This study is based on experiments performed on mice. Mice were vaccinated with the adjuvanted protein vaccines twice, 21 days apart. Mouse plasma was collected periodically, while nasal and bronchoalveolar fluids were collected 7 days after the second dose.