Mucosal surfaces are the first contact sites of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most
SARS-CoV-2 vaccines induce specific
IgG responses but provide limited mucosal immunity.
Cytokine B-cell activation factor (BAFF) and A proliferation-inducing
ligand (APRIL) in the
tumor necrosis factor (TNF) superfamily play key immunological functions during B cell development and antibody production. Furthermore, homeostatic
chemokines, such as C-X-C motif
chemokine ligand 13 (
CXCL13), chemokine (C-C motif)
ligand 19 (CCL19), and CCL21, can induce B- and T-cell responses to
infection and promote the formation of inducible bronchus-associated lymphoid tissues (iBALT), where specific local immune responses and memory cells are generated. We reviewed the role of BAFF, APRIL, CXCL13, CCL19, and CCL21 in the activation of local B-cell responses and antibody production, and the formation of iBALT in the lung following viral
respiratory infections. We speculate that mucosal
vaccines may offer more efficient protection against
SARS-CoV-2 infection than systematic
vaccines and hypothesize that a novel SARS-CoV-2
mRNA mucosal
vaccine using BAFF/APRIL or CXCL13 as
immunostimulants combined with the spike
protein-encoding
mRNA may enhance the efficiency of the local immune response and prevent the early stages of SARS-CoV-2 replication and the rapid viral clearance from the airways.