Considerations for Novel COVID-19 Mucosal Vaccine Development

Area of Science:

• Immunology
• Vaccinology
• Respiratory Infections

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects mucosal surfaces.
• Current vaccines offer limited mucosal immunity, despite inducing systemic IgG responses.
• Key immune factors like Cytokine B-cell activation factor (BAFF), A proliferation-inducing ligand (APRIL), and chemokines (CXCL13, CCL19, CCL21) are crucial for local B-cell responses and lymphoid tissue formation.

Purpose of the Study:

• To review the role of BAFF, APRIL, CXCL13, CCL19, and CCL21 in local immune responses and inducible bronchus-associated lymphoid tissue (iBALT) formation after viral respiratory infections.
• To hypothesize a novel SARS-CoV-2 mRNA mucosal vaccine strategy.

Main Methods:

• Literature review on the immunological functions of BAFF, APRIL, and specific chemokines in viral respiratory infections.
• Analysis of their roles in B-cell activation, antibody production, and iBALT formation.
• Speculation on potential vaccine strategies based on existing knowledge.

Main Results:

• BAFF, APRIL, CXCL13, CCL19, and CCL21 are vital for activating local B-cell immunity and generating iBALT.
• These factors promote the generation of specific local immune responses and memory cells in the lungs.
• Systemic vaccines may be less effective than mucosal vaccines for respiratory viruses.

Conclusions:

• Mucosal vaccines could provide superior protection against SARS-CoV-2 compared to systemic vaccines.
• A novel SARS-CoV-2 mRNA mucosal vaccine incorporating BAFF/APRIL or CXCL13 as immunostimulants alongside spike protein mRNA may enhance local immune responses.
• This approach could potentially prevent early viral replication and promote rapid viral clearance from the airways.