Abstract
Humoral immunity to SARS-CoV-2 can be supplemented with polyclonal sera from convalescent donors or an engineered monoclonal antibody (mAb) product. While pentameric IgM antibodies are responsible for much of convalescent sera’s neutralizing capacity, all available mAbs are based on the monomeric IgG antibody subtype. We now show that IgM mAbs derived from immune memory B cell receptors are potent neutralizers of SARS-CoV-2. IgM mAbs outperformed clonally identical IgG antibodies across a range of affinities and SARS-CoV-2 receptor-binding domain epitopes. Strikingly, efficacy against SARS-CoV-2 viral variants was retained for IgM but not for clonally identical IgG. To investigate the biological role for IgM memory in SARS-CoV-2, we also generated IgM mAbs from antigen-experienced IgM+ memory B cells in convalescent donors, identifying a potent neutralizing antibody. Our results highlight the therapeutic potential of IgM mAbs and inform our understanding of the role for IgM memory against a rapidly mutating pathogen.
【초록키워드】 neutralizing antibody, SARS-CoV-2, IgG, IgM, Efficacy, Immunity, monoclonal antibody, variant, memory B cells, memory, Antigen, Epitopes, Humoral immunity, IgG antibody, Viral, pathogen, IgG antibodies, immune memory, neutralizing capacity, donors, convalescent, convalescent sera, mAbs, memory B cell, affinity, Donor, mAb, B cell receptor, IgM antibody, domain, therapeutic potential, while, polyclonal sera, affinities, highlight, SARS-CoV-2 viral, responsible, retained, monomeric, 【제목키워드】 SARS-CoV-2, IgM antibody,