DataSheet_1_Vaccination with staphylococcal protein A protects mice against systemic complications of skin infection recurrences.docx

Skin and soft tissue infections (SSTIs) are the most common diseases caused by Staphylococcus aureus (S. aureus), which can progress to threatening conditions due to recurrences and systemic complications. Staphylococcal protein A (SpA) is an immunomodulator antigen of S. aureus, which allows bacterial evasion from the immune system by interfering with different types of immune responses to pathogen antigens. Immunization with SpA could potentially unmask the pathogen to the immune system, leading to the production of antibodies that can protect from a second encounter with S. aureus, as it occurs in skin infection recurrences. Here, we describe a study in which mice are immunized with a mutated form of SpA mixed with the Adjuvant System 01 (SpAmut/AS01) before a primary S. aureus skin infection. Although mice are not protected from the infection under these conditions, they are able to mount a broader pathogen-specific functional immune response that results in protection against systemic dissemination of bacteria following an S. aureus second infection (recurrence). We show that this “hidden effect” of SpA can be partially explained by higher functionality of induced anti-SpA antibodies, which promotes better phagocytic activity. Moreover, a broader and stronger humoral response is elicited against several S. aureus antigens that during an infection are masked by SpA activity, which could prevent S. aureus spreading from the skin through the blood.</p

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services