Therapy and prophylaxis of inhaled biological toxins.
This review highlights the current lack of therapeutic and prophylactic treatments for use against inhaled biological toxins, especially those considered as potential biological warfare (BW) or terrorist threats. Although vaccine development remains a priority, the use of rapidly deployable adjunctive therapeutic or prophylactic drugs could be life-saving in severe cases of intoxication or where vaccination has not been possible or immunity not established. The current lack of such drugs is due to many factors. Thus, methods involving molecular modelling are limited by the extent to which the cellular receptor sites and mode of action and structure of a toxin need to be known. There is also our general lack of knowledge of what effect individual toxins will have when inhaled into the lungs - whether and to what extent the action will be cell specific and cytotoxic or rather an acute inflammatory response requiring the use of immunomodulators. Possible sources of specific high-affinity toxin antagonists being investigated include monoclonal antibodies, selected oligonucleotides (aptamers) and derivatized dendritic polymers (dendrimers). The initial selection of suitable agents of these kinds can be made using cytotoxicity assays involving cultured normal human lung cells and a range of suitable indicators. The possibility that a mixture of selected antibody, aptamer or dendrimer-based materials for one or more toxins could be delivered simultaneously as injections or as inhaled aerosol sprays should be investigated.
Paddle
Brian M
BM
DSTO, Platforms Sciences Laboratory, 506 Lorimer Street, Fishermans Bend, Victoria 3207, Australia. brian.paddle@dsto.defence.gov.au
D000280:Administration, Inhalation; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis / Q000706:statistics & numerical data*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D001428:Bacterial Vaccines / Q000627:therapeutic use; D001694:Biological Warfare; D006801:Humans; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control*; D011634:Public Health
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D001428:Bacterial Vaccines