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Current influenza vaccines stimulate neutralising antibody to the haemagglutinin antigen but as there is antigenic drift in HA it is difficult to prepare a vaccine in advance against an emergent strain. A potential strategy is to induce CD8(+) and CD4(+) T cells that recognize epitopes within internal proteins that are less subject to antigenic drift. Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine. In this study, we evaluate the quality of influenza specific T cell responses in a clinical trial using MVA-NP+M1 vaccination followed by influenza virus challenge. In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenza HLA A*02 M158-66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells. BCL2 expression was lower in vaccinated volunteers. These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.

Background. The novel influenza vaccine MVA-NP+M1 is designed to boost cross-reactive T-cell responses to internal antigens of the influenza A virus that are conserved across all subtypes, providing protection against both influenza disease and virus shedding against all influenza A viruses. Following a phase 1 clinical study that demonstrated vaccine safety and immunogenicity, a phase 2a vaccination and influenza challenge study has been conducted in healthy adult volunteers. Methods. Volunteers with no measurable serum antibodies to influenza A/Wisconsin/67/2005 received either a single vaccination with MVA-NP+M1 or no vaccination. T-cell responses to the vaccine antigens were measured at enrollment and again prior to virus challenge. All volunteers underwent intranasal administration of influenza A/Wisconsin/67/2005 while in a quarantine unit and were monitored for symptoms of influenza disease and virus shedding. Results. Volunteers had a significantly increased T-cell response to the vaccine antigens following a single dose of the vaccine, with an increase in cytolytic effector molecules. Intranasal influenza challenge was undertaken without safety issues. Two of 11 vaccinees and 5 of 11 control subjects developed laboratory-confirmed influenza (symptoms plus virus shedding). Symptoms of influenza were less pronounced in the vaccinees and there was a significant reduction in the number of days of virus shedding in those vaccinees who developed influenza (mean, 1.09 days in controls, 0.45 days in vaccinees, P = .036). Conclusions. This study provides the first demonstration of clinical efficacy of a T-cell-based influenza vaccine and indicates that further clinical development should be undertaken. Clinical Trials Registration. NCT00993083.

A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences, yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells. We examined whether an invariant HLA-B8 restricted Nef₉₀₋₉₇ epitope FL8 shared between five high titre viruses and eight recombinant vaccinia viruses expressing Nef from different viral isolates (clades A-H) could activate antiviral activity in FL8-specific cytotoxic T-lymphocytes (CTL). Surprisingly, despite epitope conservation, we found that CTL antiviral efficacy is dependent on the infecting viral isolate. Only 23% of Nef proteins, expressed by HIV-1 isolates or as recombinant vaccinia-Nef, were optimally recognised by CTL. Recognition of the HIV-1 isolates by CTL was independent of clade-grouping but correlated with virus-specific polymorphisms in the epitope flanking region, which altered immunoproteasomal cleavage resulting in enhanced or impaired epitope generation. The finding that the majority of virus isolates failed to present this conserved epitope highlights the importance of viral variance in CTL epitope flanking regions on the efficiency of antigen processing, which has been considerably underestimated previously. This has important implications for future vaccine design strategies since efficient presentation of conserved viral epitopes is necessary to promote enhanced anti-viral immune responses.

A major challenge to developing a successful HIV vaccine is the vast diversity of viral sequences, yet it is generally assumed that an epitope conserved between different strains will be recognised by responding T-cells. We examined whether an invariant HLA-B8 restricted [Nef.sub.90-97] epitope FL8 shared between five high titre viruses and eight recombinant vaccinia viruses expressing Nef from different viral isolates (clades A-H) could activate antiviral activity in FL8-specific cytotoxic T-lymphocytes (CTL). Surprisingly, despite epitope conservation, we found that CTL antiviral efficacy is dependent on the infecting viral isolate. Only 23% of Nef proteins, expressed by HIV-1 isolates or as recombinant vaccinia-Nef, were optimally recognised by CTL. Recognition of the HIV-1 isolates by CTL was independent of clade-grouping but correlated with virusspecific polymorphisms in the epitope flanking region, which altered immunoproteasomal cleavage resulting in enhanced or impaired epitope generation. The finding that the majority of virus isolates failed to present this conserved epitope highlights the importance of viral variance in CTL epitope flanking regions on the efficiency of antigen processing, which has been considerably underestimated previously. This has important implications for future vaccine design strategies since efficient presentation of conserved viral epitopes is necessary to promote enhanced anti-viral immune responses.

Current influenza vaccines stimulate neutralising antibody to the haemagglutinin antigen but as there is antigenic drift in HA it is difficult to prepare a vaccine in advance against an emergent strain. A potential strategy is to induce CD8+ and CD4+ T cells that recognize epitopes within internal proteins that are less subject to antigenic drift. Augmenting humoral responses to HA with T cell responses to more conserved antigens may result in a more broadly protective vaccine. In this study, we evaluate the quality of influenza specific T cell responses in a clinical trial using MVA-NP+M1 vaccination followed by influenza virus challenge. In vaccinated volunteers, the expression of Granzyme A, Perforin and CD57 on influenza HLA A*02 M158-66 antigen specific cells was higher than non-vaccinated volunteers before and after challenge despite a similar frequency of antigen specific cells. BCL2 expression was lower in vaccinated volunteers. These data indicate that antigen specific T cells are a useful additional measure for use in human vaccination or immunization studies.

Dating violence (DV) is a widespread social issue that has numerous deleterious repercussions on youths’ health. Family and peer risk factors for DV have been widely studied, but with inconsistent methodologies, which complicates global comprehension of the phenomenon. Protective factors, although understudied, constitutes a promising line of research for prevention. To date, there is no comprehensive quantitative review attempting to summarize knowledge on both family and peer factors that increase or decrease the risk for adolescents and emerging adults DV victimization. The current meta-analysis draws on 87 studies with a total sample of 278,712 adolescents and young adults to examine effect sizes of the association between various family and peer correlates of DV victimization. Results suggest small, significant effect sizes for all the family (various forms of child maltreatment, parental support, and parental monitoring) and peer factors (peer victimization, sexual harassment, affiliation with deviant peers, and supportive/prosocial peers) in the prediction of DV. With few exceptions, forms of DV (psychological, physical, and sexual), gender, and age did not moderate the strength of these associations. In addition, no difference was found between the magnitude of family and peer factors’ effect sizes, suggesting that these determinants are equally important in predicting DV. The current results provide future directions for examining relations between risk and protective factors for DV and indicate that both peers and family should be part of the development of efficient prevention options.

Objective: To explore if self-reported presence of thinking about tics or body-focused repetitive behaviours (BFRBs; gests) are direct triggers of tic or gest onset in 3 groups: Tourette syndrome (TS; n =18), persistent chronic tic disorders (TDs; n = 42), and a comparison group with BFRB (n = 36). Method: The 3 groups completed a thinking about tics inventory, listing 22 items derived from clinician consensus that asked whether thoughts always, sometimes, or never exclusively triggered tic onset. Other questionnaires measured mood, perfectionism, impulsivity, premonitory urge, and self-rated tension. Sixty-three participants completed the inventory twice, and the inventory was completed pre- and post-behavioural intervention by a further 54. Results: The ranking of the thoughts reported as likely to trigger tics or gests was positively correlated across TD and BFRB groups. Exploratory principal components analysis of a reduced 12-item set (the thinking about tics inventory) in TS and TD groups revealed that such thoughts could be grouped into 3 separate subscales: thoughts about the interference of tics or gests, thoughts anticipating tics or gests, and thoughts about whether the person has permission to perform the tic or the gest. The 3 sets of subscales showed good and acceptable internal consistency and overall score showed good test–retest reliability, suggesting thoughts about tics or gests are robust and measurable. The subscales correlated with impulsivity, tic or behaviour severity, and ratings of frequency decreased post-behavioural treatment. Conclusions: Thinking about tics or gests is reported as triggering tics or gests in both TD and BFRB, and meta-cognition seems independent of premonitory sensations and relates to distinct clinical characteristics in each clinical group.

The COVID-19 pandemic and resultant containment effects has had a detrimental effect on individuals' social, occupational and financial circumstances. Taking a person-centred approach to inquiry and data analysis, we sought to identify classes (or segments) of employees with distinct configurations of responses across several pandemic-related stressors. We also investigated purported risk and resilience factors of membership in these classes. We analyzed data from 4277 employees who completed a pulse survey in August 2020, using latent class analysis to identify classes of employees with unique patterns of responses across six pandemic-related stressors. We also conducted a multinomial logistic regression analysis to explore the associations between several risk and resilience factors (e.g. age, gender, perceived organizational support) and class membership, and we compared the emergent classes' levels of self-reported mental health. The data revealed four unique classes of employees: \"adapting,\" \"conflicted,\" \"insecure\" and \" stressed\" (30%, 35%, 21% and 14% of the sample, respectively). All of the risk and resilience factors were associated with being in the adapting class versus the other classes. The adapting employees also showed the most positive self-reported mental health relative to their counterparts. By identifying classes of employees with distinct configurations of pandemic-related stressors, as well as differential risk factors and levels of self-reported mental health, the present study offers a starting point for informing work-related interventions with the goal of helping employees most vulnerable to pandemic-related stressors effectively cope with these stressors.

Previous research has shown an association between child maltreatment (sexual abuse, physical abuse, neglect, or witnessing interparental violence) and adolescent sexual risk behaviors (SRBs). The mechanisms explaining this association are not well understood, but attachment theory could provide further insight into them. This study examined the relationships between child maltreatment and SRBs and investigated anxious and avoidant attachment as mediators. The sample comprised 1,900 sexually active adolescents (13 to 17 years old; 60.8% girls) attending Quebec high schools. The results of path analyses indicated that neglect was associated with a higher number of sexual partners, casual sexual behavior, and being younger at first intercourse. Anxious attachment mediated the relation between neglect and number of sexual partners, whereas avoidant attachment explained the relation between neglect and number of sexual partners, casual sexual behavior, and age at first intercourse (for boys only). Sexual abuse was directly associated with all three SRBs. Neither anxious attachment nor avoidant attachment mediated these associations. Youth with a history of neglect and sexual abuse represent a vulnerable population that is likely to engage in SRBs. Interventions designed to induce a positive change in attachment security may reduce SRBs among victims of neglect.