A chimeric EBV gp350/220-based VLP replicates the virion B-cell attachment mechanism and elicits long-lasting neutralizing antibodies in mice

Epstein-Barr virus (EBV), an oncogenic gammaherpesvirus, causes acute infectious mononucleosis (AIM) and is linked to the development of several human malignancies. There is an urgent need for a vaccine that is safe, prevents infection and/or limits disease. Unique among human herpesviruses, glycoprotein (gp)350/220, which initiates EBV attachment to susceptible host cells, is the major ligand on the EBV envelope and is highly conserved. Interaction between gp350/220 and complement receptor type 2 (CR2)/CD21 and/or (CR1)/CD35 on B-cells is required for infection. Potent antibody responses to gp350/220 occur in animal models and humans. Thus, gp350/220 provides an attractive candidate for prophylactic subunit vaccine development. However, in a recent Phase II clinical trial immunization with soluble recombinant gp350 reduced the incidence of AIM, but did not prevent infection. Despite various attempts to produce an EBV vaccine, no vaccine is licensed. Herein we describe a sub-unit vaccine against EBV based on a novel Newcastle disease virus (NDV)-virus-like particle (VLP) platform consisting of EBVgp350/220 ectodomain fused to NDV-fusion (F) protein. The chimeric protein EBVgp350/220-F is incorporated into the membrane of a VLP composed of the NDV matrix and nucleoprotein. The particles resemble native EBV in diameter and shape and bind CD21 and CD35. Immunization of BALB/c mice with EBVgp350/220-F VLPs elicited strong, long-lasting neutralizing antibody responses when assessed in vitro. This chimeric VLP is predicted to provide a superior safety profile as it is efficiently produced in Chinese hamster ovary (CHO) cells using a platform devoid of human nucleic acid and EBV-transforming genes

Invasive acremonium strictum infection in a bone marrow transplant recipient

We describe an invasive Acremonium strictum infection in a 9-year-old debilitated bone marrow transplant recipient. Outcome was successful, despite resistance to the amphotericin B that was initially administered. A. strictum was isolated from bone and urine cultures. We summarize data on 15 opportunistic invasive infections caused by Acremonium in pediatric hosts reported thus far in the English language literature

HEPATITIS C TREATMENT CONCOMITANT TO CHEMOTHERAPY AS “SALVAGE” THERAPY IN CHILDREN WITH HEMATOLOGIC MALIGNANCIES

In patients with malignancies, chronic hepatitis C reactivation or severe flare is uncommon and antiviral treatment is deferred mainly due to underlying bone marrow and immune suppression. We report the use of antiviral treatment concomitantly to chemotherapy in 3 children with hematologic malignancies, chronic hepatitis C, and significant liver dysfunction

High serum lactate dehydrogenase adds prognostic value to the international myeloma staging system even in the era of novel agents

Objectives: High serum lactate dehydrogenase (LDH) is associated with features of advanced disease and inferior survival in multiple myeloma. It is however unclear whether LDH adds to the prognostic value of International Staging System (ISS) and whether it retains its prognostic significance in patients who are exposed to novel agent-based therapies. Patients/Methods: To address these issues we analyzed 996 consecutive symptomatic patients who were included in the database of the Greek Myeloma Study Group and received frontline treatment between January 1, 1995 and December 31, 2008. Results: The median overall survival (OS) of all patients was 40 months with a clear improvement in those who started treatment after January 1, 2000 (49 vs. 31 months; P < 0.01). A multivariate model showed that LDH, ISS, performance status, age and platelet counts had an independent prognostic value for OS (P < 0.001 for all parameters). The median OS of patients with high (11% of patients) and normal LDH was 15 vs. 44 months (P < 0.001). High LDH was associated with inferior OS within all ISS groups: 22 vs. 76 months for high and normal LDH groups, respectively, in ISS-1 (P < 0.01); 11 vs. 40 months in ISS-2 (P < 0.001) and 17 vs. 27 months in ISS-3 (P < 0.01). The median OS of high and normal LDH groups among patients who received novel agents was 21 vs. 51 months, respectively (P < 0.001). Conclusions: Lactate dehydrogenase is a readily available and inexpensive variable, which has a major impact on the survival of myeloma patients even when they belong to a low or intermediate ISS subgroup and even when they receive novel agent-based therapies