No abstract

Epitope-based vaccines designed to induce CTL responses specific for HIV-1 are being developed as a means for addressing vaccine potency and viral heterogeneity. We identified a set of 21 HLA-A2, HLA-A3, and HLA-B7 restricted supertype epitopes from conserved regions of HIV-1 to develop such a vaccine. Based on peptide-binding studies and phenotypic frequencies of HLA-A2, HLA-A3, and HLA-B7 allelic variants, these epitopes are predicted to be immunogenic in greater than 85% of individuals. Immunological recognition of all but one of the vaccine candidate epitopes was demonstrated by IFN-γ ELISPOT assays in PBMC from HIV-1-infected subjects. The HLA supertypes of the subjects was a very strong predictor of epitope-specific responses, but some subjects responded to epitopes outside of the predicted HLA type. A DNA plasmid vaccine, EP HIV-1090, was designed to express the 21 CTL epitopes as a single Ag and tested for immunogenicity using HLA transgenic mice. Immunization of HLA transgenic mice with this vaccine was sufficient to induce CTL responses to multiple HIV-1 epitopes, comparable in magnitude to those induced by immunization with peptides. The CTL induced by the vaccine recognized target cells pulsed with peptide or cells transfected with HIV-1 env or gag genes. There was no indication of immunodominance, as the vaccine induced CTL responses specific for multiple epitopes in individual mice. These data indicate that the EP HIV-1090 DNA vaccine may be suitable for inducing relevant HIV-1-specific CTL responses in humans.

Reliance on self-report limits clinicians' ability to accurately predict suicidal behavior. In this study the predictive validity of an objective measure, the death/suicide Implicit Association Test (d/sIAT), was tested among psychiatrically hospitalized veterans. Following acute stabilization, 176 participants completed the d/sIAT and traditional suicide risk assessments. Participants had similar d/sIAT scores regardless of whether they had recently attempted suicide. However, d/sIAT scores significantly predicted suicide attempts during the 6-month follow-up above and beyond other known risk factors for suicidal behavior (OR = 1.89; 95% CI: 1.15-3.12; based on 1SD increase). The d/sIAT may augment the accuracy of suicide risk assessment.

Physical activity outcomes are poor following total knee arthroplasty (TKA). The purpose was to evaluate feasibility of a physical activity feedback intervention for patients after TKA. Participants completing conventional TKA rehabilitation were randomized to a physical activity feedback (PAF; n = 22) or control (CTL; n = 23) group. The PAF intervention included real-time activity feedback, weekly action planning, and monthly group support meetings (12 weeks). The CTL group received attention control education. Feasibility was assessed using retention, adherence, dose goal attainment, and responsiveness with pre- and postintervention testing. The PAF group had 100% retention, 92% adherence (frequency of feedback use), and 65% dose goal attainment (frequency of meeting goals). The PAF group average daily step count increased from 5,754 (2,714) (pre) to 6,917 (3,445) steps/day (post). This study describes a feasible intervention to use as an adjunct to conventional rehabilitation for people with TKA.