Abstract
SARS-CoV-2 nucleocapsid protein (N) induces strong antibody (Ab) and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2-infected cells or N-expressing transfected cells binds to neighboring cells by electrostatic high-affinity binding to heparan sulfate and heparin, but not other sulfated glycosaminoglycans. N binds with high affinity to 11 human chemokines, including CXCL12β, whose chemotaxis of leukocytes is inhibited by N from SARS-CoV-2, SARS-CoV-1, and MERS-CoV. Anti-N Abs bound to the surface of N-expressing cells activate Fc receptor-expressing cells. Our findings indicate that cell surface N manipulates innate immunity by sequestering chemokines and can be targeted by Fc-expressing innate immune cells. This, in combination with its conserved antigenicity among human CoVs, advances its candidacy for vaccines that induce cross-reactive B and T cell immunity to SARS-CoV-2 variants and other human CoVs, including novel zoonotic strains.
【초록키워드】 SARS-CoV-2, Vaccine, Immunity, antibody, Innate immunity, SARS-CoV-2 variant, chemokines, heparin, SARS-CoV-1, MERS-CoV, chemokine, nucleocapsid protein, heparan sulfate, T cell, SARS-CoV-2 variants, cells, zoonotic, T cell responses, immune cells, Innate immune cells, antigenicity, Strains, leukocytes, Combination, cross-reactive, leukocyte, sulfate, live cells, infected cells, high affinity, CoVs, human CoVs, SARS-CoV-2-infected cells, chemotaxis, cytosol, neighboring cells, high-affinity binding, Cell, sequestering, bind, detect, conserved, inhibited, transfected cell, induce, activate, released, electrostatic, neighboring cell, SARS-CoV-2-infected cell, sulfated, 【제목키워드】 adaptive, Immunity, Protein, cell surface, SARS-CoV-2 nucleocapsid, modulate,