A Single Dose of BNT162b2 mRNA Vaccine Induces Airway Immunity in SARS-CoV-2 Naive and recovered COVID-19 subjects

Abstract

Background

Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior mucosal infection compared to injections of a parenteral vaccine in a mucosally naive subject. We investigated whether this was also the case for the BNT162b2 COVID-19 mRNA vaccine.

Methods

Twenty recovered COVID-19 subjects (RCS) and 23 SARS-CoV-2 naive subjects were vaccinated with respectively one and two doses of the BNT162b2 COVID-19 vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA antibody levels to Spike and for their ability to neutralize binding of Spike to ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism.

Results

All RCS had both nasal and blood SARS-CoV-2 specific antibodies at least 90 days after initial diagnosis. In RCS, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2 naive subjects after two vaccine doses compared to RCS after one dose.

Conclusion

Mucosal immune response to the SARS-CoV-2 Spike protein is higher in RCS after a single vaccine dose compared to SARS-CoV-2 naive subjects after two doses.