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Abstract
The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2- to 4-fold lower than to the homologous virus. In addition, pe
+CD27
+ B cells at each sampling time point (top). Mean frequencies of SARS-CoV-2 S-specific B cells expressing the indicated isotype in mild and severe donors (bottom). Error bars denote standard deviation and black bars indicate means. (F) Proportion of SARS-CoV-2 S-specific swIg
+ B cells that express CD71 at each sampling time point (top). Mean frequencies of SARS-CoV-2 S-specific swIg
+CD71
+ B cells in mild and severe donors (bottom). Error bars denote standard deviation and black bars indicate means. The dotted line indicates the level of CD71 expression on swIg
+ B cells in pre-pandemic donor samples. (G) Representative gating for SARS-CoV-2 S-specific B cells. The gated populations were single cell sorted for mAb cloning. Statistical comparisons between naive and convalescent donors were made by two-sided one-way Welsh ANOVA for unpaired samples with Dunnett’s T3 multiple comparisons test. Statistical comparisons between timepoints among convalescent donors were perfo
Abstract
Cancer immunotherapy with 4-1BB agonists has limited further clinical development because of dose-limiting toxicity. Here, we developed a bispecific antibody (bsAb; B7-H3×4-1BB), targeting human B7-H3 (hB7-H3) and mouse or human 4-1BB, to restrict the 4-1BB stimulation in tumors. B7-H3×m4-1BB elicited a 4-1BB–dependent antitumor response in hB7-H3–overexpressing tumor models without systemic toxicity. BsAb primarily targets CD8 T cells in the tumor and increases their proliferation and cytokine production. Among the CD8 T cell population in the tumor, 4-1BB is solely expressed on PD-1