| pathology of inhalation anthrax in cynomolgus monkeys (macaca fascicularis). | anthrax is considered a serious biowarfare and bioterrorism threat because of its high lethality, especially by the inhalation route. rhesus macaques (macaca mulatta) are the most commonly used nonhuman primate model of human inhalation anthrax exposure. the nonavailability of rhesus macaques necessitated development of an alternate model for vaccine testing and immunologic studies. this report describes the median lethal dose (ld(50)) and pathology of inhalation anthrax in cynomolgus macaques ( ... | 2003 | 12920249 |
| selection of a macaque fab with framework regions like those in humans, high affinity, and ability to neutralize the protective antigen (pa) of bacillus anthracis by binding to the segment of pa between residues 686 and 694. | human anthrax infection cannot always be treated successfully by antibiotics, as highlighted by recent bioterrorist attacks; thus, adjunct therapies are clearly needed for the future. there is a particular need to further develop adjunct therapies that can neutralize secreted toxins, such as antibodies directed towards the 83-kda protective antigen (pa(83)). in the absence of human donors, we immunized a macaque (macaca fascicularis) with pa(83) to obtain such antibodies suitable as an adjunct t ... | 2005 | 16048955 |
| high-affinity, human antibody-like antibody fragment (single-chain variable fragment) neutralizing the lethal factor (lf) of bacillus anthracis by inhibiting protective antigen-lf complex formation. | the anthrax lethal toxin (lt) consists of two subunits, the protective antigen (pa) and the lethal factor (lf), and is essential for anthrax pathogenesis. several recombinant antibodies directed against pa and intended for medical use have been obtained, but none against lf, despite the recommendations of anthrax experts. here we describe an anti-lf single-chain variable fragment (scfv) that originated from an immunized macaque (macaca fascicularis) and was obtained by phage display. panning of ... | 2007 | 17517846 |
| experimental respiratory anthrax infection in the common marmoset (callithrix jacchus). | inhalational anthrax is a rare but potentially fatal infection in man. the common marmoset (callithrix jacchus) was evaluated as a small non-human primate (nhp) model of inhalational anthrax infection, as an alternative to larger nhp species. the marmoset was found to be susceptible to inhalational exposure to bacillus anthracis ames strain. the pathophysiology of infection following inhalational exposure was similar to that previously reported in the rhesus and cynomolgus macaque and humans. th ... | 2008 | 18460069 |
| phase i study evaluating the safety and pharmacokinetics of mdx-1303, a fully human monoclonal antibody against bacillus anthracis protective antigen, in healthy volunteers. | mdx-1303 (valortim) is a fully human monoclonal antibody (hmab) with a high affinity for bacillus anthracis protective antigen (pa). mdx-1303 binds to pa and interferes with the activity of the anthrax toxin; it was selected based on its superior functional activity in the toxin neutralization activity (tna) assay. mdx-1303 has demonstrated efficacy in the postexposure and therapeutic settings in new zealand white rabbits, cynomolgus monkeys, and african green monkeys. this phase i study sought ... | 2011 | 21976227 |
| efficacy projection of obiltoxaximab for treatment of inhalational anthrax across a range of disease severity. | inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. the efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (pa), was examined in multiple studies conducted in two animal models of inhalational anthrax. a single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to new zealand white rabbits (two studies) and cynomolgus m ... | 2016 | 27431222 |
| obiltoxaximab prevents disseminated bacillus anthracis infection and improves survival during pre- and postexposure prophylaxis in animal models of inhalational anthrax. | the centers for disease control and prevention recommend adjunctive antitoxins when systemic anthrax is suspected. obiltoxaximab, a monoclonal antibody against protective antigen (pa), is approved for treatment of inhalational anthrax in combination with antibiotics and for prophylaxis when alternative therapies are not available. the impact of toxin neutralization with obiltoxaximab during pre- and postexposure prophylaxis was explored, and efficacy results that supported the prophylaxis indica ... | 2016 | 27431219 |
| evaluation of early immune response-survival relationship in cynomolgus macaques after anthrax vaccine adsorbed vaccination and bacillus anthracis spore challenge. | anthrax vaccine adsorbed (ava, biothrax) is approved by the us food and drug administration for post-exposure prophylaxis (pep) of anthrax in adults. the pep schedule is 3 subcutaneous (sc) doses (0, 14 and 28 days), in conjunction with a 60 day course of antimicrobials. the objectives of this study were to understand the onset of protection from ava pep vaccination and to assess the potential for shortening the duration of antimicrobial treatment (http://www.phe.gov/preparedness/mcm/phemce/docu ... | 2016 | 27155494 |
| a cpg-ficoll nanoparticle adjuvant for anthrax protective antigen enhances immunogenicity and provides single-immunization protection against inhaled anthrax in monkeys. | nanoparticulate delivery systems for vaccine adjuvants, designed to enhance targeting of secondary lymphoid organs and activation of apcs, have shown substantial promise for enhanced immunopotentiation. we investigated the adjuvant activity of synthetic oligonucleotides containing cpg-rich motifs linked to the sucrose polymer ficoll, forming soluble 50-nm particles (dv230-ficoll), each containing >100 molecules of the tlr9 ligand, dv230. dv230-ficoll was evaluated as an adjuvant for a candidate ... | 2016 | 26608924 |
| lethal factor, but not edema factor, is required to cause fatal anthrax in cynomolgus macaques after pulmonary spore challenge. | inhalational anthrax is caused by inhalation of bacillus anthracis spores. the ability of b. anthracis to cause anthrax is attributed to the plasmid-encoded a/b-type toxins, edema toxin (edema factor and protective antigen) and lethal toxin (lethal factor and protective antigen), and a poly-d-glutamic acid capsule. to better understand the contribution of these toxins to the disease pathophysiology in vivo, we used b. anthracis ames strain and isogenic toxin deletion mutants derived from the ame ... | 2014 | 25285720 |
| efficacy and safety of avp-21d9, an anthrax monoclonal antibody, in animal models and humans. | anthrax is an acute infectious disease caused by the spore-forming bacterium bacillus anthracis. timely administration of antibiotics approved for the treatment of anthrax disease may prevent associated morbidity and mortality. however, any delay in initiating antimicrobial therapy may result in increased mortality, as inhalational anthrax progresses rapidly to the toxemic phase of disease. an anthrax antitoxin, avp-21d9, also known as thravixa (fully human anthrax monoclonal antibody), is being ... | 2014 | 24733473 |
| development of an inhalational bacillus anthracis exposure therapeutic model in cynomolgus macaques. | appropriate animal models are required to test medical countermeasures to bioterrorist threats. to that end, we characterized a nonhuman primate (nhp) inhalational anthrax therapeutic model for use in testing anthrax therapeutic medical countermeasures according to the u.s. food and drug administration animal rule. a clinical profile was recorded for each nhp exposed to a lethal dose of bacillus anthracis ames spores. specific diagnostic parameters were detected relatively early in disease progr ... | 2012 | 22956657 |
| the fluorocycline tp-271 is efficacious in models of aerosolized bacillus anthracis infection in balb/c mice and cynomolgus macaques. | the fluorocycline tp-271 was evaluated in mouse and non-human (nhp) primate models of inhalational anthrax. balb/c mice were exposed by nose-only aerosol to 18 - 88 ld50bacillus anthracis ames spores. when 21 days of once-daily dosing was initiated at 24 hours post-challenge (post-exposure prophylaxis, pep), survival for the 3, 6, 12 and 18 mg/kg tp-271 groups was 90%, 95%, 95%, and 84%, respectively. when 21 days of dosing was initiated at 48 hours post-challenge (treatment, tx) survival for th ... | 2017 | 28784679 |
| correlation between anthrax lethal toxin neutralizing antibody levels and survival in guinea pigs and nonhuman primates vaccinated with the av7909 anthrax vaccine candidate. | the anthrax vaccine candidate av7909 is being developed as a next generation vaccine for a post-exposure prophylaxis (pep) indication against anthrax. av7909 consists of the anthrax vaccine adsorbed (ava, biothrax®) bulk drug substance adjuvanted with the immunostimulatory oligodeoxynucleotide (odn) compound, cpg 7909. the addition of cpg 7909 to ava enhances both the magnitude and the kinetics of antibody responses in animals and human subjects, making av7909 a suitable next-generation vaccine ... | 2017 | 28774566 |
| obiltoxaximab: adding to the treatment arsenal for bacillus anthracis infection. | to review the safety and efficacy of obiltoxaximab, a monoclonal antibody indicated for the treatment of bacillus anthracis inhalational anthrax in adult and pediatric patients. | 2017 | 28573869 |