Dendritic cell-based therapeutic vaccine elicits polyfunctional HIV-specific T-cell immunity associated with control of viral load.

Efforts aimed at restoring robust immune responses limiting human immunodeficiency virus (HIV)-1 replication therapeutically are warranted. We report that vaccination with dendritic cells generated ex vivo and loaded with HIV lipopeptides in patients (n = 19) on antiretroviral therapy was well tolerated and immunogenic. Vaccination increased: (i) the breadth of the immune response from 1 (1-3) to 4 (2-5) peptide-pool responses/patient (p = 0.009); (ii) the frequency of functional T cells (producing at least two cytokines among IFN-γ, TNF-α, and IL-2) from 0.026 to 0.32% (p = 0.002) and from 0.26 to 0.35% (p = 0.005) for CD4(+) and CD8(+) T cells, respectively; and (iii) the breadth of cytokines secreted by PBMCs upon antigen exposure, including IL-2, IFN-γ, IL-21, IL-17, and IL-13. Fifty percent of patients experienced a maximum of viral load (VL) 1 log10 lower than the other half following antiretroviral treatment interruption. An inverse correlation was found between the maximum of VL and the frequency of polyfunctional CD4(+) T cells (p = 0.007), production of IL-2 (p = 0.006), IFN-γ (p = 0.01), IL-21 (p = 0.006), and IL-13 (p = 0.001). These results suggest an association between vaccine responses and a better control of viral replication. These findings will help in the development of strategies for a functional cure for HIV infection.

Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine.

In the search for a therapeutic HIV-1 vaccine, we describe herein the development of a monocyte-derived dendritic cell (DC) vaccine loaded with a mixture of HIV-1-antigen lipopeptides (ANRS HIV-LIPO-5 Vaccine). LIPO-5 is comprised of five HIV-1-antigen peptides (Gag(17-35), Gag(253-284), Nef(66-97), Nef(116-145), and Pol(325-355)), each covalently linked to a palmitoyl-lysylamide moiety. Monocytes enriched from HIV-1-infected highly active antiretroviral therapy (HAART)-treated patients were cultured for three days with granulocyte-macrophage colony-stimulating factor and alpha-interferon. At day 2, the DCs were loaded with ANRS HIV-LIPO-5 vaccine, activated with lipopolysaccharide, harvested at day 3 and frozen. Flow cytometry analysis of thawed DC vaccines showed expression of DC differentiation markers: CD1b/c, CD14, HLA-DR, CD11c, co-stimulatory molecule CD80 and DC maturation marker CD83. DCs were capable of eliciting an HIV-1-antigen-specific response, as measured by expansion of autologous CD4(+) and CD8(+) T-cells. The expanded T-cells secreted gamma-IFN and interleukin (IL)-13, but not IL-10. The safety and immunogenicity of this DC vaccine are being evaluated in a Phase I/II clinical trial in chronically HIV-1-infected patients on HAART (clinicaltrials.gov identifier: NCT00796770).

Sensitivity to punishment and low maternal care account for the link between bulimic and social anxiety symptomology.

OBJECTIVE: The current study examined the joint effect of personality and parenting factors on the prediction of bulimia nervosa (BN) and social anxiety disorder (SAD) symptomology in a sample of female college students. The study also tested whether personality and parenting factors might account for the association between BN and SAD symptoms. METHOD: One-hundred twenty-eight participants completed self-report measures assessing maternal care (MC), maternal overprotection, sensitivity to punishment (SP), sensitivity to reward (SR), and BN and SAD symptomology. RESULTS: SP, SR, and MC each uniquely predicted BN symptoms, whereas only SP and MC predicted SAD symptoms. High SP interacted with low MC to predict BN and SAD symptoms over the main effects. In addition, SP, MC, and the interaction term SP x MC mediated the association between SAD and BN symptoms. CONCLUSION: High SP and low MC appear to account for the link between BN and SAD symptomology, whereas high SR appears to distinguish the disorders.

A modified DBT skills training program for oppositional defiant adolescents: promising preliminary findings.

A modified skills training component of dialectical behavior therapy (DBT) was implemented in a group therapy format for non-suicidal outpatient young adolescents who met criteria for oppositional defiant disorder (ODD). Thirty-two youths completed the 16-week program, as well as pre- and post-treatment measures. The treatment was effective not only in decreasing negative behaviors, but also in increasing positive behaviors, per caregiver report. The youths reported a significant reduction in externalizing and internalizing symptoms and in depression. Reliable change indices indicated that far more participants were in the improved category than in the deteriorated category on the measures of interest. Despite the absence of control groups but consistent with the treatment outcome research literature for DBT-based treatments for other disorders, this study demonstrated that DBT skills training is feasible and shows promise in improving the behavior of ODD young adolescents.

Correlates of posttraumatic growth in survivors of intimate partner violence.

The negative consequences of intimate partner violence are well documented. This study investigated the possibility that some survivors of intimate partner violence may also experience posttraumatic growth because of their struggle with this highly stressful circumstance. In addition, the relationships between posttraumatic growth and relationship status, type of abuse, depression, and availability of models of posttraumatic growth were examined. Most women reported posttraumatic growth. Overall abuse experienced and depression were unrelated to posttraumatic growth, but abuse was related to one domain of growth. Contact with a model of posttraumatic growth and having left an abusive relationship were both positively related to posttraumatic growth.

Studies of polyester fiber as carrier for microbes in a quantitative test method for disinfectants.

Tests were conducted by a Task Force on Disinfectant Test Methods that was appointed to investigate controversies regarding the accuracy of AOAC test methods for disinfectants as presented in AOAC's Official Methods of Analysis, Chapter 6. The general principles for new and improved AOAC tests are discussed, and a disinfectant test using microbes labeled onto a polyester fiber surface is described. The quantitative test measures the survival of test microbes as a function of exposure time as well as the exposure conditions required to kill 6 log10 of the test microbes. The time required was similar to that for the kinetics of the kill of Bacillus subtilis-labeled cylinders as tested by methods of the AOAC Sporicidal Test 966.04.