First and second hybridizations were performed on groups of 4 individual libraries using a custom set of 80-mer probes specific for EBOV

First and second hybridizations were performed on groups of 4 individual libraries using a custom set of 80-mer probes specific for EBOV. subclass antibody is usually predominant. All rhesus macaques infected with Ebola computer virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic. Keywords:Ebola; therapeutic; countermeasure; rhesus; bovine Several passive immunotherapeutics are under development to treat emerging infectious diseases and filoviruses [16]. However, traditional human-derived and heterologous animal-derived polyclonal immunoglobulins (Igs) and monoclonal antibodies can have lengthy development and/or clinical safety issues [1,7,8]. To address these shortcomings, genetically altered transchromosomic bovines (Tc-bovines) were developed that adaptively produce fully human polyclonal antibodies after exposure to environmental or vaccine antigens [912]. After hyperimmunization, Tc-bovine fully human IgG (Tc-hIgG) can be rapidly produced from their plasma [1316]. Tc-bovines, depending upon age and size, produce 150 to 600 grams of purified Tc-hIgG per month. Experimental high-titer Tc-hIgGs were produced against several pathogens and exhibited efficacy in animal models. In a recent study, 2 Tc-hIgG Investigational New Drug applications (ClinicalTrials.gov 9-Dihydro-13-acetylbaccatin III nos.NCT02788188andNCT02508584) were approved by the US Food and Drug Administration for Middle East respiratory syndrome coronavirus (MERS CoV) [17] andMycoplasma hominisindications (termed SAB-301 and SAB-136, respectively). SAB-301 was safe and well tolerated in a completed phase I clinical trial with an average terminal IgG elimination half-life (t1/2) of ~28 days (d) that is similar to human-derived intravenous Ig (IVIG) [18]. SAB-136 was safe and efficacious in a phase I clinical trial that treated a patient with severe immunodeficiency, hypogammaglobinemia, and chronicM hominisseptic hip and polyarthritis. The patient received SAB-136 for 1 year, and the drug was well tolerated with no significant adverse events and displayed and his clinical parameters improved with decreased mycoplasma burden [19]. To respond to the Ebola computer virus (EBOV) disease epidemic in Africa, 3 federal laboratories of the Mouse monoclonal to CD11b.4AM216 reacts with CD11b, a member of the integrin a chain family with 165 kDa MW. which is expressed on NK cells, monocytes, granulocytes and subsets of T and B cells. It associates with CD18 to form CD11b/CD18 complex.The cellular function of CD11b is on neutrophil and monocyte interactions with stimulated endothelium; Phagocytosis of iC3b or IgG coated particles as a receptor; Chemotaxis and apoptosis National Interagency Confederation of Biological Research at Ft. Detrick, MD [20] led a consortium to sequentially produce and evaluate 3 purified good manufacturing practices (GMP) anti-EBOV Tc-hIgGs (collectively termed SAB-139) derived from Tc-bovines hyperimmunized with a recombinant EBOV/Makona isolate glycoprotein (rGP) vaccine [21]. In a previous study, a bench-scale non-GMP lot of SAB-139 produced after the second vaccination of Tc-bovines guarded 90% of mice when administered 24 hours (h) after contamination with mouse-adapted EBOV [13]. In this study, we report SAB-139s characteristics and efficacy against EBOV contamination in a series of in vitro and rhesus macaque experiments. == METHODS == == Ethics Statement == All National Institute of Allergy and Infectious Diseases (NIAID) Integrated Research Facility (IRF) and SAB animal facilities and animal programs are accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. The study protocols were reviewed and approved 9-Dihydro-13-acetylbaccatin III by the SAB and NIAID IRF Institutional Animal Care and Use Committees in compliance with all applicable federal regulations 9-Dihydro-13-acetylbaccatin III governing the protection of animals and research. == Transchromosomic Bovine Production, Hyperimmunization, and Plasma Collection == Transchromosomic bovine production was previously described [912]. Two Tc-bovines were immunized intramuscularly (IM) with EBOV/Makona rGP (2014 Zaire variant; Novavax, Inc.) [21] formulated with SABs proprietary adjuvant SAB-adj-1. The Tc-bovines were vaccinated 8 occasions (V1V8) at 9-Dihydro-13-acetylbaccatin III 3- to 4-week (wk) intervals. The antigen dose was 2mg per animal for first vaccination (V1)V4 and 5mg per animal for V5V8. Plasma and serum samples were taken at various time points before and/or after each vaccination. Before the V1, a volume of prevaccination plasma was collected from each study Tc-bovine for use as unfavorable.