Single-cell analysis of memory B cells from top neutralizers reveals multiple sites of vulnerability within HCMV Trimer and Pentamer.

Human cytomegalovirus (HCMV) can cause severe diseases in fetuses, newborns, and immunocompromised individuals. Currently, no vaccines are approved, and treatment options are limited. Here, we analyzed the human B cell response of four HCMV top neutralizers from a cohort of 9,000 individuals. By single-cell analyses of memory B cells targeting the pentameric and trimeric HCMV surface complexes, we identified vulnerable sites on the shared gH/gL subunits as well as complex-specific subunits UL128/130/131A and gO. Using high-resolution cryogenic electron microscopy, we revealed the structural basis of the neutralization mechanisms of antibodies targeting various binding sites. Moreover, we identified highly potent antibodies that neutralized a broad spectrum of HCMV strains, including primary clinical isolates, that outperform known antibodies used in clinical trials. Our study provides a deep understanding of the mechanisms of HCMV neutralization and identifies promising antibody candidates to prevent and treat HCMV infection.

Introducing the youth residential rehabilitation service: An operational and experiential overview of a psychosocial residential support option for young people experiencing mental health challenges.

AIM: A range of residential supports is available for young people experiencing mental health challenges. One Australian example is the Youth Residential Rehabilitation Service, which provides up to 12 months of intensive psychosocial support in a residential setting to young people aged 16-25 experiencing serious mental health challenges. This paper aimed to add to the scant literature on these services, describing the experiences of young people and staff members across the duration of a stay. METHODS: This study drew on collaborative autoethnography to engage and centre the direct lived experience of young people who had lived, and staff who had worked, in a Youth Residential Rehabilitation Service. RESULTS: We identified three phases that young people typically journey through during their stay at the service. The Arriving phase was marked by appropriate referrals, a warm welcome, a period of settling in and the development of trusting relationships. The Discovering phase saw young people identifying and enacting their strengths, hopes and values. Community connections were a focus of the Continuing phase as lives after service exit were envisioned and created. CONCLUSIONS: Drawing on collaborative autoethnography methods represents one approach to amplify the voice of young people in service design and evaluation. This paper richly described some of the possibilities and complexities of the Youth Residential Rehabilitation Service experience, which can be used to inform the service's pacing and structure of support.

Co-producing to understand what matters to young people living in youth residential rehabilitation services.

AIM: Residential group care is an important service for vulnerable young people experiencing mental health, substance abuse and/or behavioural challenges. Yet little is written about specific models and their outcomes, especially from the perspectives of the young people who use these services. This project aimed to explore what matters to young people living in a 12-month voluntary residential program for young people aged 16-25. METHODS: This participatory action research study was co-produced with Youth Residential Rehabilitation Service residents and staff as co-researchers. A steering group comprising residents, staff and researchers oversaw all research stages. 18 young people and 17 staff members participated in either individual or group interviews to discuss what was important in Youth Residential Rehabilitation Services. Data analysis drew on grounded theory techniques; subsequent codes and themes were refined in the steering group. RESULTS: We identified the 'change work' that young people were expected to do, and the milieu factors that created a supportive environment. As young people were figuring out their directions and learning new skills, they needed to be understood as the developing expert of their own lives. Real relationships with staff and other young people created a culture of belonging, safety and feeling known. These findings are metaphorically captured in the image of an egg. CONCLUSIONS: Our study highlights that real relationships between all Youth Residential Rehabilitation Service community members are central to creating the atmosphere of safety and belonging that enables healing and self-development to occur.