Current Trends in Bioterrorism and Biodefense

James A Hust and Nicholas E Burgis^*

Department of Chemistry and Biochemistry, Eastern Washington University, Cheney, WA 99004, USA

*Corresponding Author:

Nicholas E Burgis
Department of Chemistry and Biochemistry
226 Science Building, Eastern Washington University
Cheney, WA 99004, USA
Tel: 509-359-7901
Fax: 509-359-6973
E-mail: nburgis@ewu.edu

Received Date: May 09, 2013; Accepted Date: May 13, 2013; Published Date: May 16, 2013

Citation: Hust JA, Burgis NE (2013) Current Trends in Bioterrorism and Biodefense. J Bioterr Biodef S3:e002. doi: 10.4172/2157-2526.S3-e002

Copyright: © 2013 Hust JA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Current trends in bioterrorism and biodefense research have resulted in the realization of cheap, effective and powerful methods of both detection and protection based biodefense strategies. For the first time, the U.S. FDA has approved a monoclonal antibody (mAb) for antibacterial uses: ABthrax for treatment of inhalational anthrax [1]. This event suggests exciting new trends in the licensing and commercial production of novel prophylactic technologies. To foster further development of emerging technologies, it is essential that funding for research programs which contribute to public health and safety remains a high priority.

Trends in biodefense strategies have aimed to fulfill unmet needs regarding the production of effective immunogenic, full-length antibodies containing human-like glycosylation patterns [2]. These moieties have been shown to affect both enzymatic proteolysis, and in vitro aggregation of therapeutic antibodies. Recent work with Ebola virus shows that mAbs with modified N-glycosylation patterns have increased potency and could potentially be used as human therapeutics [3]. Ebola virus poses significant threat as a bioterror agent due to its high level of virulence and the lack of an effective prophylactic [4]. Recent studies show a mixture of human/mouse chimeric mAbs have conferred significant levels of protection against lethal challenge in rhesus macaques. This post-exposure efficacy of an in vivo administration of mAbs in a primate model suggests its potential viability as a therapy for human exposure to Ebola virus [5].

Other trends seek to help prevent and control a range of pathogens by focusing on the ability to synthesize and deliver protective antigens. Advances in transient gene expression technologies may provide potent medical countermeasures for bioterror agents [2]. Recombinant attenuated Salmonella has the potential to revolutionize the delivery of DNA vaccines into target tissues and induce a prophylactic immune response. This modified S. typhimurium infects host tissues, where it produces a protective antigen from recombinant plasmids, which is released to the target tissues during pre-programmed cell-lysis and apoptosis. This live vaccine delivery platform has been designed to produce the HA antigen for influenza WSN virus, and resulted in complete protection for mice against lethal challenge of influenza virus [6]. Similar experiments show that antigen synthesis can be increased by inserting multiple gene cassettes into the attenuated live-vector chromosome. Using green fluorescence protein (GFP) to observe expression in target sites, models showed increased production of GFP in correlation with growth phases, suggesting that gene synthesis could be designed to integrate with the live-vaccine lifecycle to maximize effective delivery of antigen and subsequent immunogenic response [7]. A newly developed whole-cell vaccine against Yersinia pestis protects against both bubonic and pneumonic plague. Two separate virulence plasmids have been engineered to encode for both the F1 and the new V-antigen subunits, either individually or as a fused unit. Although it is not known by precisely what mechanism protection is conferred, this new vaccine has passed Phase2A human clinical trials [8]. These technological advances are expected to increase the speed and effectiveness of pathogen control, and could revolutionize biodefense strategies.

A recent U.S. patent application presents new methods for delivering vaccines: edible transgenic plants and orally administered recombinant bacteria. Lactococcus lact is encoding influenza HA is proposed to deliver protection against H5N1 virus via oral administration [9]. Foreign antigens encoded by Mycobacterium leprae have been synthesized from recombinant plasmids and administered intranasally via liposome delivery systems. Liposome nano particles function as vehicles for delivery, controlling antigen release rates, and protecting the antigen from in vivo degradation, while avoiding self-activation of the immune response. Liposome delivery systems have been shown to modulate a significant immune response to fungal infections, such as paracoccidioidomycosis, and have potential to increase the efficacy of nano biological vaccine therapy for myriad threats [10].

Early detection of a bioterror agent increases the ability of the responder to control and treat a pathogenic threat. In this area of research, the trend is to capitalize on the unique biochemistry of the infectious organism. For example, Dengue virus (DV) represents a bioterror threat, for which there is no known vaccine or effective therapy. Cellular kinases participate in the replication of DV, and have been identified through proteomic investigation. Vetter et al. [11] used uncleavable ATP- and ADP-acyl phosphate probes to ‘trap’ intracellular protein kinases, and identified increased DNA-PK activity as a characteristic of early DV serotype 2 infection. This ability to detect DV activity within 60 min of infection shows the effectiveness of chemoproteomic profiling techniques in detecting changes in cell state functions, and could aid in the development of quick pathogen detection technologies.

New approaches using mass spectrometry have been developed to detect the presence of Clostridium botulinum. Recent work using isotopically labeled oligopeptides shows that botulinum toxin A can be detected based on the proteolytic cleavage patterns of these oligopeptides. This Stable Isotope Peptide Mass Spectrometry (SIPMS) is an improvement over similar analytical methods [12]. In another study, botulinum neurotoxins A-G enzymatically cleave rat brain synaptic proteins, and the fragments can be characterized by western blot using antibodies specific to serotype. The few hours it takes to perform this new assay is much shorter than the days long mouse bioassay that is the gold standard for botulism detection [13]. Remarkably, one rat brain provides enough protein to perform millions of detection experiments, and the proteins are stable at -20°C for at least 6 months. This technology presents a widely applicable method for quick and inexpensive detection of a lethal bioterror threat.

Simultaneous detection of multiple bioterror agents allows for a more rapid response and intervention. It has been suggested that the host cytokine response to infection can be utilized to identify a pathogen [14]. Recently, a whole blood ex vivo exposure model (WEEM) was used to detect seven pathogens, including B. anthracis and 3 virulent Yersinia species present in blood samples. Here, protein profiling with antibody arrays was used to simultaneously detect 30 unique cytokines, and statistical clustering allowed correlation of cytokine levels with their causative pathogens [15]. Measuring cytokine expression via host response to infection could potentially lead to pre-symptomatic detection of pathogens, and may provide a basis for new sentinel surveillance technologies. Additionally, UK researchers are working on PCR identification of B. anthracis using new target sequences. Their methodology proved as accurate as conventional clinical blood cultures, suggesting that this technique could lead to faster identification for B. anthracis infection [16].

It is exciting to consider the myriad applications these new technologies could produce, and envision how these trends will shape future research in the fields of bioterrorism and biodefense. It is important that steady and sufficient funding is in place to ensure discovery remains on the current trajectory for these fields.

References

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