Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1.95 Å and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site.
View Article and Find Full Text PDFEliciting broadly neutralizing antibodies (bnAbs) is a cornerstone of HIV-1 vaccine strategies. Comparing HIV-1 envelope (env) sequences from the first weeks of infection to the breadth of antibody responses observed several years after infection can help define viral features critical to vaccine design. We investigated the relationship between HIV-1 env genetics and the development of neutralization breadth in 70 individuals enrolled in a prospective acute HIV-1 cohort.
View Article and Find Full Text PDFProtocols for efficient capture of antigen-specific B cells (ASBCs) are useful for understanding pathogen-specific B-cell responses during natural infection or vaccination. Fluorescently labeled tetramerized probes are classically used to capture ASBCs, but many occlude valuable epitopes available for B-cell receptor binding. Here, we describe a bead assay to confirm ASBC receptor accessibility on probes and a sequential staining process to capture HIV gp140-specific B cells from human peripheral blood mononuclear cells.
View Article and Find Full Text PDFDetermining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14-43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia.
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