Antibody gene-based prophylaxis and therapy for biodefence.
The threat from the use of biowarfare (BW)/bioterrorism (BT) agents is now more likely than ever. Antibodies, which are naturally produced molecules with high specificity and affinity, play an important role in immune defence by recognizing and eliminating invading microbial pathogens or neutralizing toxins. Passive antibody administration is an effective means of conferring immediate immunity to a susceptible host for post-exposure prophylaxis or therapy of BW/BT agent-mediated diseases, but the immunity would not last long and antibody production is a lengthy, labor intensive, and expensive process. An alternative approach is to take advantage of the body's natural ability to express transgenes to produce passive antibodies. This approach can be achieved by the in vivo delivery of genes encoding BW/BT agent-specific antibodies for biodefence applications. It is also possible to design antibody fragments to be expressed inside a cell via antibody gene delivery for combating intracellular BW/BT agents and toxins, which natural antibodies cannot reach. Animal studies have shown that the expressed antibodies can be detected as early as day 3, reaches peak levels at day 7, and maintains therapeutic levels in serum for more than seven months after a single administration via antibody gene delivery. Therefore, antibody gene delivery in vivo might be a new approach for post-exposure prophylaxis or therapy and for pre-exposure prophylaxis (vaccination) of BW/BT agent-mediated diseases although there are still some problems to be overcome before this new approach can actually be used in humans.
Hu
Wei-Gang
WG
Defense Research and Development Canada-Suffield, Alberta, Canada. wei-gang.hu@drdc-rddc.gc.ca <wei-gang.hu@drdc-rddc.gc.ca>
Nagata
Les P
LP
D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D001694:Biological Warfare / Q000517:prevention & control*; D016503:Drug Delivery Systems; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007128:Immunoglobulin Fragments / Q000627:therapeutic use; D014777:Virus Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology
D000906:Antibodies; D007128:Immunoglobulin Fragments