Protective immunity induced by an inhaled SARS-CoV-2 subunit vaccine

Area of Science:

• Immunology
• Vaccinology
• Respiratory Virology

Background:

• Current COVID-19 vaccines are administered intramuscularly, which may not optimally target the respiratory tract, the primary site of SARS-CoV-2 infection.
• Developing vaccines that induce local mucosal immunity is crucial for enhancing protection against respiratory viruses.

Purpose of the Study:

• To evaluate the efficacy of ISR52, an inhaled subunit vaccine candidate based on the SARS-CoV-2 Spike S1 protein, in inducing protective mucosal immune responses.
• To compare the protective effects of intranasal/intratracheal administration of ISR52 with subcutaneous injection in a mouse model.

Main Methods:

• Utilized a lethal challenge hACE2 transgenic mouse model for SARS-CoV-2 infection.
• Administered ISR52 via intranasal, intratracheal, and subcutaneous routes.
• Assessed immune responses including T-cell (CD4, CD8), antibody (IgG, IgA), and neutralizing antibody levels in lungs and serum.
• Evaluated protection against severe infection.

Main Results:

• Intranasal and intratracheal administration of ISR52 provided superior protection against severe SARS-CoV-2 infection compared to subcutaneous injection.
• Inhaled ISR52 elicited durable Spike-specific CD4 and CD8 T-cell responses for at least 6 months in wild-type mice.
• Induced IgG and IgA responses cross-reacted with SARS-CoV-2 variants of concern, and protected animals had neutralizing antibodies in lungs and serum.

Conclusions:

• Inhaled administration of the SARS-CoV-2 Spike S1 subunit vaccine candidate ISR52 effectively induces local and systemic immune responses, offering superior protection compared to conventional intramuscular vaccination.
• ISR52 is being developed as a dry powder formulation for inhalation, potentially eliminating the need for cold-chain storage and needle administration.
• These findings support the advancement of ISR52 into Phase I/II clinical trials for a needle-free, cold-chain-independent COVID-19 vaccine.