An Intranasal OMV-Based Vaccine Induces High Mucosal and Systemic Protecting Immunity Against a SARS-CoV-2 Infection

Area of Science:

• Vaccinology
• Immunology
• Virology

Background:

• Current COVID-19 vaccines (mRNA, viral vector, inactivated virus) are primarily intramuscular, inducing systemic immunity.
• Emerging SARS-CoV-2 variants necessitate improved vaccine strategies, including those inducing mucosal immunity to block transmission.
• Intranasal vaccine administration offers advantages in ease of use, cost-effectiveness, and targeting the respiratory tract's primary entry point.

Purpose of the Study:

• To develop and evaluate a novel intranasal subunit vaccine for COVID-19.
• To assess the immunogenicity and protective efficacy of the OMV-mC-Spike vaccine in preclinical models.

Main Methods:

• Development of a subunit vaccine (OMV-mC-Spike) using a stabilized SARS-CoV-2 spike protein linked to Neisseria meningitidis outer membrane vesicles (OMVs).
• Prime-boost vaccination of mice and hamsters via intranasal or intramuscular routes.
• Assessment of serum and mucosal antibody responses (IgG, IgA), and challenge of vaccinated hamsters with live SARS-CoV-2.

Main Results:

• Intranasal OMV-mC-Spike vaccination induced robust systemic and mucosal (serum, nasal, lung) antibody responses, including neutralizing antibodies.
• Intramuscular vaccination primarily induced serum IgG, lacking significant mucosal immunity.
• Intranasally vaccinated hamsters were protected from SARS-CoV-2-induced weight loss and lung viral replication, with no observed lung pathology.

Conclusions:

• The intranasal OMV-mC-Spike vaccine is a promising needle-free, non-replicating subunit vaccine candidate.
• Intranasal administration effectively elicits mucosal immunity, crucial for blocking SARS-CoV-2 entry and transmission.
• Further clinical development is warranted for this novel vaccine approach to combat the COVID-19 pandemic.