RESUMEN
Combat exposure among military personnel results in increased risk of posttraumatic stress disorder (PTSD), major depression, substance use, and related health risks. PTSD symptoms require innovative approaches to promote effective coping postdeployment. PTSD's nature and scope requires an approach capable of integrating multiple health risks while reaching large populations. This article provides the rationale and approach to adapt and evaluate a Pro-Change computerized tailored intervention (CTI) targeted at behavioral sequelae (i.e., smoking, stress, and depression) for veterans with or at risk for PTSD. The three-phase approach includes: 1) focus groups to review and, subsequently, adapt content of the existing CTI programs; 2) usability testing; and 3) feasibility testing using a three-month pre-postdesign. Effective, theory-based, real-time, multiple behavior interventions targeting veterans' readiness to quit smoking, manage stress, and depression are warranted to provide potential health impact, opportunities for learning veteran-specific issues, and advance multiple health behavior change knowledge.
RESUMEN
Broadly cross-reactive monoclonal antibodies define epitopes for vaccine development against HIV and other highly mutable viruses. Crystal structures are available for several such antibody-epitope complexes, but methods are needed to translate that structural information into immunogens that re-elicit similar antibodies. We describe a general computational method to design epitope-scaffolds in which contiguous structural epitopes are transplanted to scaffold proteins for conformational stabilization and immune presentation. Epitope-scaffolds designed for the poorly immunogenic but conserved HIV epitope 4E10 exhibited high epitope structural mimicry, bound with higher affinities to monoclonal antibody (mAb) 4E10 than the cognate peptide, and inhibited HIV neutralization by HIV+ sera. Rabbit immunization with an epitope-scaffold induced antibodies with structural specificity highly similar to mAb 4E10, an important advance toward elicitation of neutralizing activity. The results demonstrate that computationally designed epitope-scaffolds are valuable as structure-specific serological reagents and as immunogens to elicit antibodies with predetermined structural specificity.