Design and characterization of HIV-1 vaccine candidates to elicit antibodies targeting multiple epitopes.

A primary goal in the development of an AIDS vaccine is the elicitation of broadly neutralizing antibodies (bNAbs) that protect against diverse HIV-1 strains. To this aim, germline-targeting immunogens have been developed to activate bNAb precursors and initiate the induction of bNAbs. While most pre-clinical germline-targeting HIV-1 vaccine candidates only target a single bNAb precursor epitope, an effective HIV-1 vaccine will likely require bNAbs that target multiple epitopes on Env.

Cross-reactive sarbecovirus antibodies induced by mosaic RBD-nanoparticles.

Therapeutic monoclonal antibodies (mAbs) against SARS-CoV-2 become obsolete as spike substitutions reduce antibody binding. To induce antibodies against conserved receptor-binding domain (RBD) regions for protection against SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD-nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles.

Structures of ATP-binding cassette transporter ABCC1 reveal the molecular basis of cyclic dinucleotide cGAMP export.

Cyclic nucleotide GMP-AMP (cGAMP) plays a critical role in mediating the innate immune response through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Recent studies showed that ATP-binding cassette subfamily C member 1 (ABCC1) is a cGAMP exporter. The exported cGAMP can be imported into uninfected cells to stimulate a STING-mediated innate immune response.

Stroke recurrence and all-causemortality in CPAP-treated sleep-disordered-breathing patients.

Background: Obstructive sleep apnea (OSA) affects about 70 % of stroke patients and is closely linked to stroke development. It is unclear whether treatment with continuous positive airway pressure (CPAP) reduces the risk of stroke recurrence or mortality in post-stroke patients, partly due to limited follow-up time and small sample sizes of previous studies. To close this knowledge gap, this study investigated changes in stroke recurrence and mortality among CPAP-treated post-stroke patients with sleep-disordered breathing.