Targeted nasal vaccination provides antibody-independent protection against Staphylococcus aureus.

Despite showing promise in preclinical models, anti-Staphylococcus aureus vaccines have failed in clinical trials. To date, approaches have focused on neutralizing/opsonizing antibodies; however, vaccines exclusively inducing cellular immunity have not been studied to formally test whether a cellular-only response can protect against infection. We demonstrate that nasal vaccination with targeted nanoparticles loaded with Staphylococcus aureus antigen protects against acute systemic S. aureus infection in the absence of any antigen-specific antibodies. These findings can help inform future developments in staphylococcal vaccine development and studies into the requirements for protective immunity against S. aureus.

Suppression of antigen-specific T cell responses by the Kaposi's sarcoma-associated herpesvirus viral OX2 protein and its cellular orthologue, CD200.

Regulating appropriate activation of the immune response in the healthy host despite continual immune surveillance dictates that immune responses must be either self-limiting and therefore negatively regulated following their activation or prevented from developing inappropriately. In the case of antigen-specific T cells, their response is attenuated by several mechanisms, including ligation of CTLA-4 and PD-1. Through the study of the viral OX2 (vOX2) immunoregulator encoded by Kaposi's sarcoma-associated herpesvirus (KSHV), we have identified a T cell-attenuating role both for this protein and for CD200, a cellular orthologue of the viral vOX2 protein. In vitro, antigen-presenting cells (APC) expressing either native vOX2 or CD200 suppressed two functions of cognate antigen-specific T cell clones: gamma interferon (IFN-γ) production and mobilization of CD107a, a cytolytic granule component and measure of target cell killing ability. Mechanistically, vOX2 and CD200 expression on APC suppressed the phosphorylation of ERK1/2 mitogen-activated protein kinase in responding T cells. These data provide the first evidence for a role of both KSHV vOX2 and cellular CD200 in the negative regulation of antigen-specific T cell responses. They suggest that KSHV has evolved to harness the host CD200-based mechanism of attenuation of T cell responses to facilitate virus persistence and dissemination within the infected individual. Moreover, our studies define a new paradigm in immune modulation by viruses: the provision of a negative costimulatory signal to T cells by a virus-encoded orthologue of CD200.

An exploration of the professional identity of clinical academics using repertory grid technique.

BACKGROUND: Clinicians who divide their time between clinical work and research have contributed to some of the most fundamental breakthroughs in medicine in recent history, yet their role is not always well-understood or valued. Understanding the factors which contribute to career success for clinical academics is critical for supporting this workforce. Social Cognitive Career Theory (SCCT) provides a conceptual framework for career success, incorporating personal and environmental factors. PURPOSE: The aim of this study is to explore clinical academics' construal of successful clinical academic practice and to contribute to a holistic view of the professional identity of the clinical academic. METHODOLOGY: Using a constructivist technique, repertory grid, the authors interviewed ten clinical academics at different career stages in one-to-one structured interviews conducted virtually between November 2020 and April 2021. Data from the interviews were analysed qualitatively and quantitatively. Common themes were identified, analysed, and ranked according to importance with respect to successful clinical academic practice. Using SCCT as a framework, constructs were categorised as personal factors, organisational factors, competencies and person-environment fit. A differential analysis between established/trainee and female/male participants was carried out. SUMMARY OF RESULTS: One hundred and thirty-three constructs were elicited and categorised into 20 themes (constructs). There was consensus among participants that 6 were of high importance with respect to successful clinical academic practice, 8 of intermediate and 4 of low importance, with no consensus on 2 constructs. Personal factors of high importance include innovation and integrity. Competencies including research and teaching skills are highly important, and ability to collaborate is also considered central to successful clinical academic practice. Female participants expressed greater concerns about the impact of familial responsibilities on career progression. DISCUSSION AND CONCLUSIONS: This study highlights the importance of interactions between the person and environment, and characterises the important attributes of successful clinical academics including personal factors such as integrity and innovation.