Lysosomal Trafficking and Degradation of Extracellular Proteins via Multivalent Small Molecule Ligand Display on Dextran Scaffolds.

Targeted protein degradation (TPD) marks a shift in drug development from conventional inhibition to the complete removal of pathological proteins. Traditional TPD technologies target intracellular proteins of interest (POIs) for degradation but are ineffective against extracellular cell surface and soluble proteins, a significant portion of the human proteome. Recent advances involve the formation of ternary complexes between a POI and a cell surface lysosomal trafficking receptor, directing POIs to lysosomes for degradation.

CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity.

Cancer vaccines aim at generating cytotoxic CD8 T cells that kill cancer cells and confer durable tumor regression. Hereto, CD8 peptide epitopes should be presented by antigen presenting cells to CD8 T cells in lymphoid tissue. Unfortunately, in unformulated soluble form, peptide antigens are poorly taken up by antigen presenting cells and do not efficiently reach lymph nodes.

Profiling Bacteria in the Lungs of Patients with Severe Influenza Versus COVID-19 with or without Aspergillosis.

The influence of the lung bacterial microbiome, including potential pathogens, in patients with influenza-associated pulmonary aspergillosis (IAPA) or coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA) has yet to be explored. To explore the composition of the lung bacterial microbiome and its association with viral and fungal infection, immunity, and outcome in severe influenza versus COVID-19 with or without aspergillosis. We performed a retrospective study in mechanically ventilated patients with influenza and COVID-19 with or without invasive aspergillosis in whom BAL for bacterial culture (with or without PCR) was obtained within 2 weeks after ICU admission.

Lipid Nanoparticle Delivery Alters the Adjuvanticity of the TLR9 Agonist CpG by Innate Immune Activation in Lymphoid Tissue.

Pharmacological strategies to activate innate immune cells are of great relevance in the context of vaccine design and anticancer immune therapy, to mount broad immune responses able to clear infection and malignant cells. Synthetic CpG oligodeoxynucleotides (CpG-ODNs) are short single-stranded DNA molecules containing unmethylated CpG dinucleotides and a phosphorothioate backbone. Class B CpG ODNs activate robust innate immune responses through a TLR9-dependent NF-κB signaling pathway.

High Burden of COVID-19-Associated Pulmonary Aspergillosis in Severely Immunocompromised Patients Requiring Mechanical Ventilation.

Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is a frequent superinfection in critically ill patients with COVID-19 and is associated with increased mortality rates. The increasing proportion of severely immunocompromised patients with COVID-19 who require mechanical ventilation warrants research into the incidence and impact of CAPA during the vaccination era.

Methods: We performed a retrospective, monocentric, observational study.