Lethal Antibody Enhancement of Dengue Disease in Mice Is Prevented by Fc Modification

Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate DV infection of myeloid cells in vitro by promoting virus entry via Fcγ receptors (FcγR), a process known as antibody-dependent enhancement (ADE). However, despite decades of investigation, no in vivo model for antibody enhancement of dengue disease severity has been described. Analogous to human infants who receive anti-DV antibodies by transplacental transfer and develop severe dengue disease during primary infection, we show here that passive administration of anti-DV antibodies is sufficient to enhance DV infection and disease in mice using both mouse-adapted and clinical DV isolates. Antibody-enhanced lethal disease featured many of the hallmarks of severe dengue disease in humans, including thrombocytopenia, vascular leakage, elevated serum cytokine levels, and increased systemic viral burden in serum and tissue phagocytes. Passive transfer of a high dose of serotype-specific antibodies eliminated viremia, but lower doses of these antibodies or cross-reactive polyclonal or monoclonal antibodies all enhanced disease in vivo even when antibody levels were neutralizing in vitro. In contrast, a genetically engineered antibody variant (E60-N297Q) that cannot bind FcγR exhibited prophylactic and therapeutic efficacy against ADE-induced lethal challenge. These observations provide insight into the pathogenesis of antibody-enhanced dengue disease and identify a novel strategy for the design of therapeutic antibodies against dengue

Blue-Emitting InP/GaP/ZnS Quantum Dots with Enhanced Stability by Siloxane Capping: Implication for Electroluminescent Devices

InP quantum dots (QDs) with low toxicity are an ideal alternative to Cd-based QDs. However, the optical properties and stability of blue-emitting InP QDs are far inferior to those of red and green QDs. In this work, we report the synthesis of highly fluorescent InP/GaP/ZnS core/shell/ shell QDs with an emission wavelength of 484 nm and photoluminescence quantum yield of 71%, along with a full width at half-maximum as narrow as 45 nm. In addition, we encapsulated the QDs with siloxane via specific ligand exchange and condensation reactions to improve their stability. The corresponding siloxane capping QD light-emitting device (QLED) shows a maximum luminance of 690 Cd m(-2), an external quantum efficiency of 0.09%, and a much longer lifetime than pristine QDs. As a result, these enable the siloxane capping QDs to achieve a much stronger storage stability and a longer QLED lifetime than pristine QDs

Enhancement of hEPO delivery into the brain tissues by MBs/FUS.

<p>hEPO and MBs were intravenously administered and FUS was transcranially applied. (A) Rat brains were perfused and sliced into sections at 3 h after hEPO injection. Sonicated region of the brain was dissected and quantified. The hEPO levels in sections 3 and 4 were significantly higher in the I/R+hEPO+MBs/FUS group compared to the I/R+hEPO group (n = 3 for each). Data were given as means ± S.E.M., * p<0.05, as compared with the I/R+hEPO group. (B) CSF was sampled at 3 h after hEPO injection. The hEPO concentration of CSF in the I/R+hEPO+MBs/FUS group showed significant enhancement compared with the I/R+hEPO group. (C) The serum hEPO was also sampled at 3 h after hEPO injection. No hEPO was found in the sham and I/R groups without hEPO injection.</p

hEPO+MBs/FUS inhibits the ischemia/reperfusion-induced neuronal death and inflammation in rat experiments.

<p>Immunohistochemical staining of NeuN, CD-11b, and GFAP was performed 24 h after I/R. (A) illustrated the position of FUS sonication. In NeuN staining (B, E, and H), the I/R group showed a marked loss of neurons, whereas, neurons were intact in the sham and I/R+hEPO+MBs/FUS groups. In CD-11b staining (C, F, and I), the I/R group showed microglia activation (condensed nuclei), whereas the sham and I/R+hEPO+MBs/FUS groups showed ramified microglia. In GFAP staining (D, G, and J), there was an increase of GFAP in the I/R group but not in the sham and I/R+hEPO+MBs/FUS groups. (Scale bar  =  200 µm).</p

Improvement in catwalk automated gait analysis test by hEPO plus MBs/FUS in chronic phase of 3VO.

<p>Two gait analysis parameters, paw intensity (A) and paw angle (B), were assessed from Day-7 to Day-28 after I/R. In both paw intensity and paw angle, treatment with hEPO+MBs/FUS significantly improved the performance of impaired limb. Data were shown as mean ± SEM (n = 5 for each group), * p<0.05 as compared with the sham (control group), # p<0.05 as compared with the I/R group.</p

HBsAg Profiles in Patients Receiving Peginterferon Alfa-2a plus Ribavirin for the Treatment of Dual Chronic Infection with Hepatitis B and C Viruses

Background. With use of peginterferon alfa-2a and ribavirin combination therapy in patients with dual chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, 11.2% of patients achieved clearance of hepatitis B surface antigen (HBsAg) at 6 months after treatment; however, reactivation of HBV DNA was observed in 36.3%. We investigated the predictive potential of HBsAg quantification. Methods. HBsAg quantification was performed in 120 e antigen-negative patients dually infected with HBV and hepatitis C virus and treated with peginterferon alfa-2a/ribavirin for 48 weeks (HCV genotype 1; ) or n p 74 24 weeks (HCV genotype 2/3; ). HBsAg was quantified at baseline, week 4, week 12, end of treatment, and n p 46 24 weeks after treatment. Results. The baseline median serum HBsAg level was 120 IU/mL and decreased gradually during treatment. Low baseline HBsAg was significantly associated with HBsAg clearance (40% for HBsAg level р20 IU/mL vs 2.2% for HBsAg level 120 IU/mL; ). A decrease in HBsAg level from baseline to week 12 of 50% was associated P ! .05 with a reduced likelihood of HBV DNA reactivation in patients with baseline undetectable serum HBV DNA (positive predictive value, 89.5%). Conclusions. HBsAg quantification appears to be a useful indicator of posttreatment outcome in patients dually infected with HBV and hepatitis C virus