Strategies for the Prevention of a Successful Biological Warfare Aerosol Attack

Wiener, Stanley L.

doi:10.1093/milmed/161.5.251

Cited by 46 publications

(30 citation statements)

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“…Although natural infection in developed countries is rare, there has been renewed interest in F. tularensis as a human pathogen due to its potential as a biowarfare weapon (39). F. tularensis live vaccine strain (LVS) is an attenuated strain of F. tularensis that produces a lethal disease in mice quite similar to the disease in humans infected with fully virulent F. tularensis (3,13,16,35).…”

mentioning

confidence: 99%

Susceptibility to SecondaryFrancisella tularensisLive Vaccine Strain Infection in B-Cell-Deficient Mice Is Associated with Neutrophilia but Not with Defects in Specific T-Cell-Mediated Immunity

2001

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Previous studies have demonstrated a role for B cells, not associated with antibody production, in protection against lethal secondary infection of mice with Francisella tularensis live vaccine strain (LVS). However, the mechanism by which B cells contribute to this protection is not known. To study the specific role of B cells during secondary LVS infection, we developed an in vitro culture system that mimics many of the same characteristics of in vivo infection. Using this culture system, we showed that B cells do not directly control LVS infection but that control of LVS growth is mediated primarily by LVS-primed T cells. Importantly, B cells were not required for the generation of effective memory T cells since LVS-primed, B-cell-deficient (BKO) mice generated CD4؉ and CD8 ؉ T cells that controlled LVS infection similarly to LVS-primed CD4 ؉ and CD8 ؉ T cells from wild-type mice. The control of LVS growth appeared to depend primarily on gamma interferon and nitric oxide and was similar in wild-type and BKO mice. Rather, the inability of BKO mice to survive secondary LVS infection was associated with marked neutrophil influx into the spleen very early after challenge. The neutrophilia was directly associated with B cells, since BKO mice reconstituted with naive B cells prior to a secondary challenge with LVS had decreased bacterial loads and neutrophils in the spleen and survived.

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confidence: 99%

Susceptibility to SecondaryFrancisella tularensisLive Vaccine Strain Infection in B-Cell-Deficient Mice Is Associated with Neutrophilia but Not with Defects in Specific T-Cell-Mediated Immunity

2001

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“…Ricin, from the castor bean plant Ricinus communis, is a class II ribosome-inactivating protein that has the potential of being used as a weapon in a biological attack (4,5). Once inside a cell, ricin is extremely toxic; one resident molecule is sufficient to kill the cell, and the enzyme has been reported to inactivate 1777 ribosomes min Ϫ1 (2).…”

mentioning

confidence: 99%

In Vitro Selection of RNA Molecules That Inhibit the Activity of Ricin A-chain

Hesselberth

Miller

Robertus

et al. 2000

Journal of Biological Chemistry

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The cytotoxin ricin disables translation by depurinating a conserved site in eukaryotic rRNA. In vitro selection has been used to generate RNA ligands (aptamers) specific for the catalytic ricin A-chain (RTA). The anti-RTA aptamers bear no resemblance to the normal RTA substrate, the sarcin-ricin loop (SRL), and were not depurinated by RTA. An initial 80-nucleotide RNA ligand was minimized to a 31-nucleotide aptamer that contained all sequences and structures necessary for interacting with RTA. This minimal RNA formed high affinity complexes with RTA (K d ‫؍‬ 7.3 nM) which could compete directly with the SRL for binding to RTA. The aptamer inhibited RTA depurination of the SRL and could partially protect translation from RTA inhibition. The IC 50 of the aptamer for RTA in an in vitro translation assay is 100 nM, roughly 3 orders of magnitude lower than a small molecule inhibitor of ricin, pteroic acid, and 2 orders of magnitude lower than the best known RNA inhibitor. The novel anti-RTA aptamers may find application as diagnostic reagents for a potential biological warfare agent and hold promise as scaffolds for the development of strong ricin inhibitors.Ribosome-inactivating proteins inhibit protein synthesis by disabling the translation machinery. Class I ribosome-inactivating proteins have a catalytic A-chain that recognizes and depurinates a universally conserved adenosine found in a GAGA tetraloop in the sarcin-ricin loop (SRL) 1 of eukaryotic 23-28 S rRNA (1, 2). Class II ribosome-inactivating proteins have an additional lectin B-chain that is required for cell surface attachment and subsequent endocytosis of the toxin domain (3).Ricin, from the castor bean plant Ricinus communis, is a class II ribosome-inactivating protein that has the potential of being used as a weapon in a biological attack (4, 5). Once inside a cell, ricin is extremely toxic; one resident molecule is sufficient to kill the cell, and the enzyme has been reported to inactivate 1777 ribosomes min Ϫ1 (2). Aerosolized ricin causes severe respiratory distress and is lethal when injected intravenously at a level of only 3-5 g/kg (6). Ricin has so far proved to be a relatively inefficient biological weapon but is prepared easily even by Third World nations and terrorist groups. Therefore, facile detection of the toxin and the development of antidotes remain priorities (6, 7).In vitro selection is a powerful molecular tool that can be used to generate ligands for a wide variety of targets, including both nucleic acid and non-nucleic acid-binding proteins (8, 9). Aptamers can be engineered readily to function as either therapeutics or sensors. For instance, RNA aptamers that bind to human immunodeficiency virus type I Rev also inhibit viral replication (10). Similarly, RNA aptamers that bind to the ␤ 2 integrin leukocyte function-associated antigen 1 specifically inhibit a signal transduction pathway when expressed in vivo (11). Consequently, aptamers that recognize and potentially inhibit ricin might be useful prophylactic or therapeutic agent...

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“…Also, the wearing of protective equipment is required during exposure or threat of exposure to chemical, biological, radiological or nuclear agents, or unknown agent or agents, when the route of exposure may be inferred from the presence of contaminant on the clothing and skin of victims, while enabling these people to accomplish their assigned missions. Military protection equipment refers to (EMS; Iacobidze et al, 2003;SLAC, 2009;Wiener, 1996): • protection respiratory devices: rubbery masks for the protection of the respiratory tract, eyes, and mucous membranes, providing protection against vapors involved in chemical warfare and against biological warfare particles; • garment ensembles, giving protection against chemical and biological warfare agents and radioactive alpha and beta particles; • wraps, chemical-and biological-protective for casualties in contaminated environments in which personnel are unable to wear battledress overgarments, the top of the garment having a charcoal lining similar to the BDO, while the bottom being constructed of impermeable rubber; • individual ballistic protection equipment, against different fragments, splinters and small caliber projectiles, against shock waves from different explosive devices, shells and projectiles; fire-resistant garment;…”

Section: Staff Protection Equipmentmentioning

confidence: 99%

Biopolymers for Military Use: Opportunities and Environment Implications - a Review

Zecheru¹

2010

Biopolymers

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Strategies for the Prevention of a Successful Biological Warfare Aerosol Attack

Cited by 46 publications

References 0 publications

Susceptibility to SecondaryFrancisella tularensisLive Vaccine Strain Infection in B-Cell-Deficient Mice Is Associated with Neutrophilia but Not with Defects in Specific T-Cell-Mediated Immunity

Susceptibility to SecondaryFrancisella tularensisLive Vaccine Strain Infection in B-Cell-Deficient Mice Is Associated with Neutrophilia but Not with Defects in Specific T-Cell-Mediated Immunity

In Vitro Selection of RNA Molecules That Inhibit the Activity of Ricin A-chain

Biopolymers for Military Use: Opportunities and Environment Implications - a Review

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