Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• SARS-CoV-2 mRNA vaccines induce systemic immunity, but their effectiveness in the respiratory tract, especially against variants of concern (VOCs) like Omicron, remains unclear.
• Understanding immune responses in the respiratory tract is crucial for preventing SARS-CoV-2 infection and transmission.

Purpose of the Study:

• To compare SARS-CoV-2 S-specific antibody and B/T cell immunity in the blood and bronchoalveolar lavage fluid (BAL) of mRNA-vaccinated individuals versus COVID-19 convalescents.
• To evaluate the efficacy of systemic mRNA vaccination alone versus combined systemic and mucosal immunization against SARS-CoV-2, including Omicron, in a mouse model.

Main Methods:

• Comparative analysis of S-specific total and neutralizing antibodies, and B/T cell immunity in BAL and blood from vaccinated individuals and convalescents.
• Mouse immunization model using systemic mRNA vaccination and/or mucosal adenovirus-S immunization to assess respiratory tract immunity.

Main Results:

• mRNA vaccination elicited lower neutralizing antibody levels in BAL against D614G, Delta, and Omicron BA.1.1 compared to convalescents, despite robust blood responses.
• Systemic mRNA vaccination induced circulating S-specific B and T cells but not in the BAL, unlike in convalescents.
• Mouse model showed systemic mRNA vaccination alone induced weak mucosal immunity against Omicron, while combined vaccination enhanced neutralizing antibody responses.

Conclusions:

• Current mRNA vaccines are effective against severe COVID-19 by leveraging circulating immune cells but offer limited protection against breakthrough infections, particularly Omicron.
• Mucosal vaccination strategies are essential for developing comprehensive sterilizing immunity in the respiratory tract against SARS-CoV-2 and future VOCs.