Open-Source Custom Beads for Single-Cell Transcriptomics

Open-source single-cell genomics technologies have helped democratize single-cell genomics and expedite method development. Methods such as inDrops and Drop-seq for single-cell RNA-seq preceded popular technologies such as the 10x Genomics’ Chromium platform, however despite initial enthusiasm for open-source methods, their popularity has waned. A major reason has been the lack of availability of low-cost, customizable beads, which are essential for microfluidics based single-cell RNA-seq. We address this challenge by introducing a new method for producing barcoded hydrogel beads for single-cell RNA-seq called HiPER (High-throughput PER-barcoded hydrogel beads) that allows for increasing the diversity of barcode sequences, reducing manufacturing cost, and that can be readily adapted to custom applications. HiPER barcodes are decoupled from the capture sequences and can therefore be configured to capture RNA, DNA, or tailored for specific-gene enrichment

Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses

While five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1–Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern

Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses

While five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1–Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern