Screening and Identification of an H-2Kb-Restricted CTL Epitope within the Glycoprotein of Hantaan Virus.

The cytotoxic T lymphocyte (CTL) response plays a key role in controlling viral infection, but only a few epitopes within the HTNV glycoprotein (GP) that are recognized by CTLs have been reported. In this study, we identified one murine HTNV GP-derived H2-Kb-restricted CTL epitope in C57BL/6 mice, which could be used to design preclinical studies of vaccines for HTNV infection. First, 15 8-mer peptides were selected from the HTNV GP amino acid sequence based on a percentile rank of <=1% by IEDB which is the most comprehensive collection of epitope prediction and analysis tool. A lower percentile rank indicates higher affinity and higher immune response. In the case of the consensus method, we also evaluated the binding score of peptide-binding affinity by the BIMAS software to confirm that all peptides were able to bind H2-Kb. Second, one novel GP-derived CTL epitope, GP6 aa456-aa463 (ITSLFSLL), was identified in the splenocytes of HTNV-infected mice using the IFN-γ ELISPOT assay. Third, a single peptide vaccine was administered to C57BL/6 mice to evaluate the immunogenic potential of the identified peptides. ELISPOT and cell-mediated cytotoxicity assays showed that this peptide vaccine induced a strong IFN-γ response and potent cytotoxicity in immunized mice. Last, we demonstrated that the peptide-vaccinated mice had partial protection from challenge with HTNV. In conclusion, we identified an H2-Kb-restricted CTL epitope with involvement in the host immune response to HTNV infection.

Incorporation of GM-CSF or CD40L Enhances the Immunogenicity of Hantaan Virus-Like Particles.

A safe and effective Hantaan virus (HTNV) vaccine is highly desirable because HTNV causes an acute and often fatal disease (hemorrhagic fever with renal syndrome, HFRS). Since the immunity of the inactivated vaccine is weak and the safety is poor, HTNV virus-like particles (VLPs) offer an attractive and safe alternative. These particles lack the viral genome but are perceived by the immune system as virus particles. We hypothesized that adding immunostimulatory signals to VLPs would enhance their efficacy. To accomplish this enhancement, we generated chimeric HTNV VLPs containing glycosylphosphatidylinositol (GPI)-anchored granulocyte macrophage colony-stimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity in vitro. The immunization of mice with chimeric HTNV VLPs containing GM-CSF or CD40L induced stronger humoral immune responses and cellular immune responses compared to the HTNV VLPs and Chinese commercial inactivated hantavirus vaccine. Chimeric HTNV VLPs containing GM-CSF or CD40L also protected mice from an HTNV challenge. Altogether, our results suggest that anchoring immunostimulatory molecules into HTNV VLPs can be a potential approach for the control and prevention of HFRS.

Child maltreatment syndrome: demographics and developmental issues of inpatient cases

<p><b>INTRODUCTION</b>This study aimed to describe the demographic, social, developmental and behavioural profile of children hospitalised for alleged child maltreatment syndrome (CMS).</p><p><b>METHODS</b>This study was a retrospective review of the consecutive inpatient records of children (0-16 years) admitted to the National University Hospital, Singapore, for alleged CMS over a three-year period. Descriptive data on the demographic characteristics, alleged maltreatment, medical and developmental histories, and family background of these children were collected and analysed. Chi-square statistics were used to test whether family factors were associated with the type of maltreatment and the presence of developmental disorders.</p><p><b>RESULTS</b>A total of 89 children, who accounted for 90 admission cases, were studied. Physical abuse (70.0%) was the most common, followed by neglect (11.1%) and sexual abuse (7.8%). Child protection services had already been involved in 29.2% of the cases prior to the child's admission. Children who were victims of abuse were more likely to come from homes with a prior history of domestic violence (p = 0.028). Financial difficulty was found to be a risk factor for neglect (p = 0.005). Among the 89 children, 15.7% were found to have developmental disorders and 10.1% had mental health diagnoses. Children who had developmental disorders were more likely to have a parent with a mental health disorder (p = 0.002).</p><p><b>CONCLUSION</b>A sizeable proportion of the children admitted for alleged CMS had developmental or behavioural disorders. Clinicians have a role in ensuring that these children have appropriate follow-up plans. Children from high-risk families should be screened for maltreatment.</p>