Development of a guinea pig inhalational anthrax model for evaluation of post-exposure prophylaxis efficacy of anthrax vaccines.

Development of a guinea pig inhalational anthrax model for evaluation of post-exposure prophylaxis efficacy of anthrax vaccines. Vaccine. 2020 Feb 03;: Authors: Perry MR, Ionin B, Barnewall RE, Vassar ML, Reece JJ, Park S, Lemiale L, Skiadopoulos MH, Shearer JD, Savransky V Abstract A next-generation anthrax vaccine candidate, AV7909, is being developed for post-exposure prophylaxis (PEP) of inhalational anthrax in combination with the recommended course of antimicrobial therapy. Clinical efficacy studies of anthrax countermeasures in humans are not ethical or feasible, therefore, licensure of AV7909 for PEP is being pursued under the US Food and Drug Administration (FDA) Animal Rule, which requires that evidence of effectiveness be demonstrated in an animal model of anthrax, where results of studies in such a model can establish reasonable likelihood of AV7909 to produce clinical benefit in humans. Initial development of a PEP model for inhalational anthrax included evaluation of post-exposure ciprofloxacin pharmacokinetics (PK), tolerability and survival in guinea pigs treated with various ciprofloxacin dosing regimens. Three times per day (TID) intraperitoneal (IP) dosing with 7.5 mg/kg of ciprofloxacin initiated 1 day following inhalational anthrax challenge and continued for 14 days was identified as a well tolerated partially curative ciprofloxacin treatment regimen. The added benefit of AV7909 vaccination was evaluated in guinea pig...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research

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ellecchia Processing of certain viral proteins and bacterial toxins by host serine proteases is a frequent and critical step in virulence. The coronavirus spike glycoprotein contains three (S1, S2, and S2′) cleavage sites that are processed by human host proteases. The exact nature of these cleavage sites, and their respective processing proteases, can determine whether the virus can cross species and the level of pathogenicity. Recent comparisons of the genomes of the highly pathogenic SARS-CoV2 and MERS-CoV, with less pathogenic strains (e.g., Bat-RaTG13, the bat homologue of SARS-CoV2) identified possible ...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Analytical ChemistryDOI: 10.1021/acs.analchem.0c01090
Source: Analytical Chemistry - Category: Chemistry Authors: Source Type: research
I live-tweeted a fascinating and perhaps rather depressing meeting with William Haseltine via a Reuters Newsmaker Broadcast. His talk was upbeat but the message does not offer a positive outlook unless we can collaborate internationally to identify, trace, and isolate and go back to early antivirals to treat people urgently. A vaccine will probably never be found, we must stay on top of this virus when we get communities under control. Moreover, we must recognise that another emergent pathogen could appear any time. These are essentially my notes from Haseltines’s talk. Might we ever achieve herd immunity? There is n...
Source: David Bradley Sciencebase - Songs, Snaps, Science - Category: Science Authors: Tags: Sciencebase Source Type: blogs
I live-tweeted a fascinating and perhaps rather depressing meeting with William Haseltine via a Reuters Newsmaker Broadcast. His talk was upbeat but the message does not offer a positive outlook unless we can collaborate internationally to identify, trace, and isolate and go back to early antivirals to treat people urgently. A vaccine will probably never be found, we must stay on top of this virus when we get communities under control. Moreover, we must recognise that another emergent pathogen could appear any time. These are essentially my notes from Haseltines’s talk. Might we ever achieve herd immunity? There is n...
Source: David Bradley Sciencebase - Songs, Snaps, Science - Category: Science Authors: Tags: Sciencebase Source Type: blogs
In this study, we investigate the rapid and striking priming-independent LT-induced release of IL-1β in mice within hours of toxin challenge. We find IL-1β release to be a NLRP1b- and caspase-1-dependent, NLRP3 and caspase-11-independent event that requires both neutrophils and peptidyl arginine deiminiase-4 (PAD4) activity. The simultaneous LT-induced IL-18 response is neutrophil-independent. Bone marrow reconstitution experiments in mice show toxin-induced IL-1β originates from hematopoietic cells. LT treatment of neutrophils in vitro did not induce IL-1β, neutrophil extracellular traps (NETs), o...
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Tags: J Leukoc Biol Source Type: research
FG Abstract Capillary morphogenesis gene 2 (CMG2/ANTXR2) is a cell surface receptor for both collagen VI and anthrax toxin. Biallelic loss-of-function mutations in CMG2 lead to a severe condition, hyaline fibromatosis syndrome (HFS). We have here dissected a network of dynamic interactions between CMG2 and various actin interactors and regulators, describing a different behavior from other extracellular matrix receptors. CMG2 binds talin, and thereby the actin cytoskeleton, only in its ligand-free state. Extracellular ligand binding leads to src-dependent talin release and recruitment of the actin cytoskeleton re...
Source: Developmental Cell - Category: Cytology Authors: Tags: Dev Cell Source Type: research
Here’s betting you wouldn’t want anyone blowing smallpox scabs up your nose. But you might feel differently if you lived in 15th century China. Long ago, the Chinese recognized that people who had contracted smallpox once were immune to reinfection. They came up with the idea of preserving scabs from individuals who had suffered mild cases, drying them out, crushing them to a powder and blowing them up the nostril. For boys it was the right nostril, for girls it was the left because, well, 15th century. That is how the story of vaccines usually begins, though that version is decidedly incomplete. For one thing,...
Source: TIME: Science - Category: Science Authors: Tags: Uncategorized COVID-19 Explainer health Source Type: news
by Susann Dupke, Grit Schubert, F élicité Beudjé, Anne Barduhn, Maude Pauly, Emmanuel Couacy-Hymann, Roland Grunow, Chantal Akoua-Koffi, Fabian H. Leendertz, Silke R. KleeBacillus cereus biovaranthracis (Bcbva) is an untypical anthrax-causing pathogen responsible for high wildlife mortality in Ta ï National Park (TNP), Côte d’Ivoire. However, nothing is known about its effect on the rural population living in the region bordering TNP. Contact to bushmeat is a known risk factor for exposure to a variety of zoonotic pathogens, but no human infections withBcbva were noted so far. Therefor...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Abstract The blood exhibits a dynamic flux of proteins that are secreted by the tissues and cells of the body. To identify novel aging-related circulating proteins, we compared the plasma proteomic profiles of young and old mice using tandem mass spectrometry. The expression of 134 proteins differed between young and old mice. We selected seven proteins that were expressed at higher levels in young mice, and confirmed their plasma expression in immunoassays. The plasma levels of anthrax toxin receptor 2 (ANTXR2), cadherin-13 (CDH-13), scavenger receptor cysteine-rich type 1 protein M130 (CD163), cartilage oligomer...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
ACS Chemical BiologyDOI: 10.1021/acschembio.9b01027
Source: ACS Chemical Biology - Category: Chemistry Authors: Source Type: research
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