Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10 10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10 10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov , NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more t...

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Schools worldwide have implemented many different peer-led interventions with mixed results, but the evidence base on their effectiveness as mental health interventions remains limited. This study combines a scoping review and systematic review to map the variations of peer-led interventions in schools and to evaluate the quality of the existing evidence base. This scoping review and systematic review evaluated the existing literature across 11 academic databases. Studies were included if they reported a peer-led intervention that aimed to address a mental health or wellbeing issue using a peer from the same school setting. Data were extracted from published and unpublished reports and presented as a narrative synthesis. 54 studies met eligibility criteria for the scoping review, showing that peer-led interventions have been used to address a range of mental health and wellbeing issues globally. 11 studies met eligibility criteria for the systematic review with a total of 2,239 participants eligible for analysis (929 peer leaders; 1,310 peer recipients). Two studies out of seven that looked at peer leaders showed significant improvements in self-esteem and social stress, with one study showing an increase in guilt. Two studies out of five that looked at peer recipient outcomes showed significant improvements in self-confidence and in a quality of life measure, with one study showing an increase in learning stress and a decrease in overall mental health scores. The findings from these reviews show that despite widespread use of peer-led interventions, the evidence base for mental health outcomes is sparse. There appear to be better documented benefits of participation for those who are chosen and trained to be a peer leader, than for recipients. However, the small number of included studies means any conclusions about effectiveness are tentative.

Mucosal surfaces are the primary sites for the transmission of infectious agents including viruses, so effective vaccines generally should induce mucosal immunity. Furthermore, noninvasive delivery is desirable because of the ease of application, the high degree of patient compliance, and the improved safety for patients and clinicians due to the elimination of needles. Unfortunately, most of the conventional vaccines are parenterally administered and result in systemic rather than mucosal immunity. Here we present the first report of mucosal immunity by noninvasive DNA immunization in a target species. As an approach to induce mucosal immunity against bovine herpesvirus-1, cows were immunized intravaginally with suppositories containing plasmid coding for glycoprotein D. Serum IgG, as well as IgA both in the serum and in the nasal fluids, were detected, which supports the contention of a common mucosal immune system. This level of immunity was of sufficient magnitude to minimize weight loss and significantly reduce the duration of virus shedding after intranasal viral challenge, which demonstrates the efficacy of suppository-based administration of DNA vaccines to target species. As this is a very practical method of delivery, it has great potential to be applied as vaccine or therapy in a variety of species.

In response to the need for a safe, efficacious vaccine that provides broad immune protection against SARS-CoV-2 infection, we have developed a dual-antigen COVID-19 vaccine. The vaccine delivers both the viral spike (S) protein modified to increase cell-surface expression (S-Fusion) and the viral nucleocapsid (N) protein with an Enhanced T-cell Stimulation Domain (N-ETSD) to enhance MHC class I and II presentation and T-cell responses. The vaccine antigens are delivered using a human adenovirus serotype 5 (hAd5) platform with E1, E2b, and E3 regions deleted that has been shown in previous cancer vaccine studies to be effective in the presence of pre-existing hAd5 immunity. Here, we demonstrate the hAd5 S-Fusion + N-ETSD (hAd5 S + N) vaccine antigens when expressed by dendritic cells (DCs) of previously SARS-CoV-2-infected patients elicit Th1 dominant activation of autologous patient T cells, indicating the vaccine antigens have the potential for generating immune responses in patients previously infected or vaccinated. We further demonstrate that participants in our open-label Phase 1b study of the dual-antigen hAd5 S + N vaccine generate Th1 dominant S- and N-specific T cells after a single prime subcutaneous injection and that the magnitude of these responses were comparable to those seen for T cells from previously infected patients. We further present our in silico prediction of T-cell epitope HLA binding for both the first-wave SARS-CoV-2 ‘A’ strain and the K417N, E484K, and N501Y S as well as the T201I N variants that suggests T-cell responses to the hAd5 S + N vaccine will retain efficacy against these variants. These findings that the dual-antigen hAd5 S + N vaccine elicits SARS-CoV-2-relevant T-cell responses and that such cell-mediated protection is likely to be sustained against emerging variants supports the testing of this vaccine as a universal booster that would enhance and broaden existing immune protection conferred by currently approved S-based vaccines.

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Background Recent estimates suggest that one in ten young people worldwide experiences a diagnosable mental health disorder, with many more suffering subsyndromal levels of psychological distress. As young people spend much of their time in schools, the role of educational settings in the delivery of mental health provision is increasingly recognised. Advances in neurodevelopmental research have highlighted the important and complex role of peer influence on adolescent behaviours, suggesting peer-led support schemes have high potential utility. Schools worldwide have implemented peer-led interventions with mixed results, but the global evidence base on their effectiveness remains limited. This systematic review aims to examine the evidence base of the outcomes of school-based peer-led interventions on the mental health of young people aged 4–18. Methods Eligible studies will be randomised controlled trials and observational studies that report on the mental health outcomes of a peer-led school-based intervention. Eligible participants will be aged 4–18 and will be current students of the intervention school. Individual- and group-based interventions will be included. The following 11 databases will be screened based upon their reach in healthcare and education: PsycINFO, MEDLINE, EMBASE, CINAHL, CENTRAL, BEI, Scopus, Web of Science, ERIC, SSCI and Social Care Online. There will be no restriction placed on publication period, original language or country of publication. Papers will be systematically screened for eligibility by two review authors. Data will be presented as a descriptive report. A meta-analysis will be carried out if a subset of studies allows, given the anticipated high levels of heterogeneity. Discussion This systematic review will be the first to synthesise the global evidence on the mental health outcomes of peer-led interventions for children and adolescents in a school setting. It will analyse the available data in order to understand the role of these interventions in schools, inform future developers of peer support programmes and identify gaps in current research. This review will be of value to policy makers, health and education services, researchers and those involved in delivering peer support initiatives. Systematic review registration PROSPERO CRD42018116243 Electronic supplementary material The online version of this article (10.1186/s13643-019-1027-3) contains supplementary material, which is available to authorized users.