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Monoclonal antibodies that target SARS-CoV-2 with high affinity are valuable for a wide range of biomedical applications involving novel coronavirus disease (COVID-19) diagnosis, treatment, and prophylactic intervention. Strategies for the rapid and reliable isolation of these antibodies, especially potent neutralizing antibodies, are critical toward improved COVID-19 response and informed future response to emergent infectious diseases. In this study, single B cell screening was used to interrogate antibody repertoires of immunized mice and isolate antigen-specific IgG1⁺memory B cells. Using these methods, high-affinity, potent neutralizing antibodies were identified that target the receptor-binding domain of SARS-CoV-2. Further engineering of the identified molecules to increase valency resulted in enhanced neutralizing activity. Mechanistic investigation revealed that these antibodies compete with ACE2 for binding to the receptor-binding domain of SARS-CoV-2. These antibodies may warrant further development for urgent COVID-19 applications. Overall, these results highlight the potential of single B cell screening for the rapid and reliable identification of high-affinity, potent neutralizing antibodies for infectious disease applications.

Cell membranes have recently gained attention as a promising drug delivery system. Here, dendritic cell membrane vesicles (DC‐MVs) are examined as a platform to promote T cell responses. Nanosized DC‐MVs are derived from DCs pretreated with monophosphoryl lipid A (MPLA), a FDA‐approved immunostimulatory adjuvant. These “mature” DC‐MVs activate DCs in vitro and increase their expression of costimulatory markers. DC‐MVs also promote cross‐priming of antigen‐specific T cells in vitro, increasing their survival and CD25 expression. In addition, these mature DC‐MVs potently augment the expansion of adoptively transferred CD8+ T cells in vivo, generating twofold to fourfold higher frequency of antigen‐specific T cells, compared with other control formulations, including “immature” DC‐MVs obtained without the MPLA pretreatment. Taken together, these results suggest that DC‐MVs are an effective delivery platform for T cell activation and may serve as a potential delivery system for improving adoptive T cell therapy.

Extracellular traps (ETs), such as neutrophil extracellular traps, are a physical mesh deployed by immune cells to entrap and constrain pathogens. ETs are immunogenic structures composed of DNA, histones, and an array of variable protein and peptide components. While much attention has been paid to the multifaceted function of these structures, mechanistic studies of ETs remain challenging due to their heterogeneity and complexity. Here, a novel DNA‐histone mesostructure (DHM) formed by complexation of DNA and histones into a fibrous mesh is reported. DHMs mirror the DNA‐histone structural frame of ETs and offer a facile platform for cell culture studies. It is shown that DHMs are potent activators of dendritic cells and identify both the methylation state of DHMs and physical interaction between dendritic cells and DHMs as key tuning switches for immune stimulation. Overall, the DHM platform provides a new opportunity to study the role of ETs in immune activation and pathophysiology.