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.

Immune cell distribution and DNA methylation signatures differ between tumor and stroma enriched compartment in pancreatic ductal adenocarcinoma.

The presence of abundant tumor stroma is a prominent characteristic of pancreatic ductal adenocarcinomas (PDAC) that potentially influences disease progression and therapy response. This study aims to investigate immune cell infiltration and epigenetic profiles in tumor cell enriched ("Tumor") and stroma cell enriched ("Stroma") regions within human PDAC tissue samples. By comparing those regions, we identified 25,410 differentially methylated positions (DMPs) distributed across 6,963 unique genes.

DNA Methylation Signatures Correlate with Response to Immune Checkpoint Inhibitors in Metastatic Melanoma.

Background: DNA methylation profiles have emerged as potential predictors of therapeutic response in various solid tumors.

Objective: This study aimed to analyze the DNA methylation profiles of patients with stage IV metastatic melanoma undergoing first-line immune checkpoint inhibitor treatment and evaluate their correlation with a radiological response according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).

Methods: A total of 81 tissue samples from 71 patients with metastatic melanoma (27 female, 44 male) were included in this study.

SARS-CoV-2 spike glycosylation affects function and neutralization sensitivity.

The glycosylation of viral envelope proteins can play important roles in virus biology and immune evasion. The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) includes 22 N-linked glycosylation sequons and 17 O-linked glycosites. We investigated the effect of individual glycosylation sites on SARS-CoV-2 S function in pseudotyped virus infection assays and on sensitivity to monoclonal and polyclonal neutralizing antibodies.