Ebola virus (EBOV) causes severe hemorrhagic fever for which there is no approved treatment or preventive vaccine. Immunological correlates of protective immunity against EBOV disease are not well understood. However, non-human primate studies have associated protection of experimental vaccines with binding and neutralizing antibodies to the EBOV glycoprotein (GP) as well as EBOV GP-specific CD4(+) and CD8(+) T cells. In this report a full length, unmodified Zaire EBOV GP gene from the 2014 EBOV Makona strain (EBOV/Mak) was cloned into a baculovirus vector. Recombinant EBOV/Mak GP was produced in Sf9 insect cells as glycosylated trimers and, when purified, formed spherical 30-40 nm particles. In mice, EBOV/Mak GP co-administered with the saponin adjuvant Matrix-M was significantly more immunogenic, as measured by virus neutralization titers and anti-EBOV/Mak GP IgG as compared to immunization with AlPO4 adjuvanted or non-adjuvanted EBOV/Mak GP. Similarly, antigen specific T cells secreting IFN-γ were induced most prominently by EBOV/Mak GP with Matrix-M. Matrix-M also enhanced the frequency of antigen-specific germinal center B cells and follicular helper T (TFH) cells in the spleen in a dose-dependent manner. Immunization with EBOV/Mak GP with Matrix-M was 100% protective in a lethal viral challenge murine model; whereas no protection was observed with the AlPO4 adjuvant and only 10% (1/10) mice were protected in the EBOV/Mak GP antigen alone group. Matrix-M adjuvanted vaccine induced a rapid onset of specific IgG and neutralizing antibodies, increased frequency of multifunctional CD4+ and CD8(+) T cells, specific TFH cells, germinal center B cells, and persistence of EBOV GP-specific plasma B cells in the bone marrow. Taken together, the addition of Matrix-M adjuvant to the EBOV/Mak GP nanoparticles enhanced both B and T-cell immune stimulation which may be critical for an Ebola subunit vaccine with broad and long lasting protective immunity.

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ovavax reported that, in 28 days following public release of the avian influenza A/Anhui/1/2013 (H7N9) virus gene sequences, its recombinant DNA and baculovirus-Spodoptera frugiperda cell culture-based technology was used to produce a virus-like particle vaccine to avian influenza A(H7N9) virus, and murine animal challenge studies were initiated. [1] This report describes Novavax's manufacturing process and the coordinated timing of critical activities necessary to produce and release a clinical batch of avian influenza A(H7N9) virus virus-like particle vaccine, under current good manufacturing practices, within three months from the time that the virus genomic sequences for this potential pandemic influenza virus were reported. The key enabling factors were: • A detailed, integrated project plan and daily coordination meetings • Advanced use of the baculovirus master virus seed to bypass production of the passage 3 virus stock • Successful functional testing of the master virus seed to establish process parameters • Drug substance quantitation with an alternate method prior to availability of single radial immunodiffusion assay reagents • Forward processing of intermediates prior to completion of quality control testing • A process that uses single-use manufacturing technology This project has been funded in whole or in part with federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (BARDA), Department of Health and Human Services, under Contract No. HHSO100201100012C.

Olanzapine is an antipsychotic medication linked to the development, or exacerbation of, type 2 diabetes mellitus. This report describes 3 patients being treated with olanzapine who died suddenly and unexpectedly with hyperglycemic ketoacidosis. All had olanzapine concentrations within the therapeutic range. Vitreous glucose concentrations ranged from 640 mg/dL to 833 mg/dL, and blood acetone concentrations from 25.6 mg/dL to 57.6 mg/dL. Beta-hydroxybutyrate concentrations in blood were from 55.2 mg/dL to 110 mg/dL. Low levels of isopropanol were also detected. None had a history or family history of diabetes mellitus. Glycolated (A1C) hemoglobin in 2 cases was 14.3% and 14.7%. No predisposing factors to olanzapine-induced diabetes were identified. It is recommended that chemical testing of patients dying suddenly while being treated with antipsychotic drugs include vitreous glucose and blood acetone determinations to elucidate the cause and mechanism of death in these patients. Warnings concerning this potentially fatal complication of olanzapine therapy should be included in standard pharmaceutical and prescription references.