Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses and can augment early immune responses and contribute to protection. We hypothesized that MAIT cells may have inherent adjuvant activity in vaccine platforms that use replication-incompetent adenovirus vectors. In mice and humans, ChAdOx1 (chimpanzee adenovirus Ox1) immunization robustly activated MAIT cells. Activation required plasmacytoid dendritic cell (pDC)–derived interferon (IFN)–α and monocyte-derived interleukin-18. IFN-α–induced, monocyte-derived tumor necrosis factor was also identified as a key secondary signal. All three cytokines were required in vitro and in vivo. Activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers and MAIT cell–deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. Thus, MAIT cells contribute to the immunogenicity of adenovirus vectors, with implications for vaccine design.

Introduction Paediatric consultations form a significant proportion of all consultations in ambulatory care. Point-of-care tests (POCTs) may offer a potential solution to improve clinical outcomes for children by reducing diagnostic uncertainty in acute illness, and streamlining management of chronic diseases. However, their clinical impact in paediatric ambulatory care is unknown. We aimed to describe the clinical impact of all in-vitro diagnostic POCTs on patient outcomes and healthcare processes in paediatric ambulatory care. Methods We searched MEDLINE, EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from inception to 29 January 2020 without language restrictions. We included studies of children presenting to ambulatory care settings (general practice, hospital outpatient clinics, or emergency departments, walk-in centres, registered drug shops delivering healthcare) where in-vitro diagnostic POCTs were compared to usual care. We included all quantitative clinical outcome data across all conditions or infection syndromes reporting on the impact of POCTs on clinical care and healthcare processes. Where feasible, we calculated risk ratios (RR) with 95% confidence intervals (CI) by performing meta-analysis using random effects models. Results We included 35 studies. Data relating to at least one outcome were available for 89,439 children of whom 45,283 had a POCT across six conditions or infection syndromes: malaria (n = 14); non-specific acute fever 'illness' (n = 7); sore throat (n = 5); acute respiratory tract infections (n = 5); HIV (n = 3); and diabetes (n = 1). Outcomes centred around decision-making such as prescription of medications or hospital referral. Pooled estimates showed that malarial-POCTs (Plasmodium falciparum) better targeted antimalarial treatment by reducing over-treatment by a third compared to usual care (RR 0.67; 95% CI [0.58 to 0.77],

Effective communication, co-operation and teamwork have been identified as key determinants of patient safety. SBAR (Situation, Background, Assessment and Recommendation) is a structured method for communicating critical information that requires immediate attention and action. It contributes to effective escalation of management and increased patient safety and is recommended by the World Health Organization (WHO) [1] and the UK National Health Service.[2]

19Mucosal-associated invariant T (MAIT) cells can be activated by viruses through a cytokine-20 dependent mechanism, and thereby protect from lethal infection. Given this, we reasoned 21 MAIT cells may have a critical role in the immunogenicity of replication-incompetent 22 adenovirus vectors, which are novel and highly potent vaccine platforms. In vitro, ChAdOx1 23 (Chimpanzee Adenovirus Ox1) induced potent activation of MAIT cells. Activation required 24 transduction of monocytes and plasmacytoid dendritic cells to produce IL-18 and IFN-a, 25 respectively. IFN-a-induced monocyte-derived TNF-a was identified as a novel intermediate 26 in this activation pathway, and activation required combinatorial signaling of all three 27 cytokines. Furthermore, ChAdOx1-induced in vivo MAIT cell activation in both mice and 28 human volunteers. Strikingly, MAIT cell activation was necessary in vivo for development of 29ChAdOx1-induced HCV-specific CD8 T cell responses. These findings define a novel role for 30