SARS-CoV-2 protein shows promise for future vaccines

 ALBERTO DOMINGO LÓPEZ-MUÑOZ HTTPS://ORCID.ORG/0000-0003-1542-2153IVAN KOSIK HTTPS://ORCID.ORG/0000-0001-5756-5182JAROSLAV HOLLYAND JONATHAN W. YEWDELL

DOI: 10.1126/sciadv.abp9770

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.

https://www.science.org/doi/10.1126/sciadv.abp9770