Emerging antibody products and Nicotiana manufacturing.

Antibody based products are not widely available to address multiple global health challenges due to high costs, limited manufacturing capacity, and long manufacturing lead times. Nicotiana-based manufacturing of antibody products may now begin to address these challenges as a result of revolutionary advances in transient expression and altered glycosylation pathways. This review provides examples of emerging antibody-based products (mucosal and systemic) that could be competitive and commercially viable when the attributes of Nicotiana-based manufacturing (large scale, versatile, rapid, low cost) are utilized.

Risks posed by mystery illness.

Patients may present with unknown illness caused by accidental or deliberate release of biological, chemical or radioactive material or a new/emerging disease. Nurses must be aware of the protocols to follow to ensure their own safety and that of other patients. This article discusses the national advice in dealing with incidents or outbreaks of unusual illness.

Recombinant human polyclonal antibodies: A new class of therapeutic antibodies against viral infections.

The mammalian immune system eliminates pathogens by generating a specific antibody response. Polyclonality is a key feature of this immune response: the immune system produces antibodies which bind to different structures on a given pathogen thereby increasing the likelihood of its elimination. The vast majority of current recombinant antibody drugs rely on monospecific monoclonal antibodies. Inherently, such antibodies do not represent the benefits of polyclonality utilized by a natural immune system and this has impeded the identification of efficacious antibody drugs against infectious agents, including viruses. The development of novel technologies has allowed the identification and manufacturing of antigen-specific recombinant polyclonal human antibodies, so-called symphobodies. This review describes the rationale for designing drugs based on symphobodies against pathogenic viruses, including HIV, vaccinia and smallpox virus, and respiratory syncytial virus.

Potential for detection of explosive and biological hazards with electronic terahertz systems.

The terahertz (THz) regime (0.1-10 THz) is rich with emerging possibilities in sensing, imaging and communications, with unique applications to screening for weapons, explosives and biohazards, imaging of concealed objects, water content and skin. Here we present initial surveys to evaluate the possibility of sensing plastic explosives and bacterial spores using field-deployable electronic THz techniques based on short-pulse generation and coherent detection using nonlinear transmission lines and diode sampling bridges. We also review the barriers and approaches to achieving greater sensing-at-a-distance (stand-off) capabilities for THz sensing systems. We have made several reflection measurements of metallic and non-metallic targets in our laboratory, and have observed high contrast relative to reflection from skin. In particular, we have taken small quantities of energetic materials such as plastic explosives and a variety of Bacillus spores, and measured them in transmission and in reflection using a broadband pulsed electronic THz reflectometer. The pattern of reflection versus frequency gives rise to signatures that are remarkably specific to the composition of the target, even though the target's morphology and position is varied. Although more work needs to be done to reduce the effects of standing waves through time-gating or attenuators, the possibility of mapping out this contrast for imaging and detection is very attractive.

What can spores do for us?

Many organisms have the ability to form spores, a remarkable phase in their life cycles. Compared with vegetative cells, spores have several advantages (e.g. resistance to toxic compounds, temperature, desiccation and radiation) making them well suited to various applications. The applications of spores that first spring to mind are bio-warfare and the related, but more positive, field of biological control. Although they are often considered metabolically inert, spores can also be used as biocatalysts. Other uses for spores are found in the fields of probiotics, tumour detection and treatment, biosensing and in the "war against drugs".

The Army chemical/biological SMART (SMART-CB) team: the nurse's role.

A chemical or biologic attack probably will be covert, rather than overt. Because presenting signs and symptoms may mimic minor nonspecific illnesses or naturally produced disease syndromes and may not appear for several days, it is likely that nurses in emergency rooms and primary care settings will be among the first to come into contact with victims of a chemical or biologic agent exposure. Early recognition, reporting, decontamination, self-protection, prophylaxis, and treatment are imperative. After the terrorist attack on September 11, 2001, the anthrax incidents, and the heightened publicity of chemical and biologic agent attacks brought on by media coverage, the need for highly trained and well-prepared medical personnel has increased dramatically. Army nurses have led the way in training and expanding the capabilities of specialized medical response teams. Team members require ongoing training, state-of-the-art protective equipment and medical supplies, and constant practice to maintain the high state of readiness required to respond rapidly and effectively to chemical or biologic threats. Army SMART-CB nurses and their team members are well prepared to provide lifesaving care in highly contaminated areas. It is no longer a question of if but rather when and where the next attack will occur.

An integrated, stacked microlaboratory for biological agent detection with DNA and immunoassays.

An integrated, stacked microlaboratory for performing automated electric-field-driven immunoassays and DNA hybridization assays was developed. The stacked microlaboratory was fabricated by orderly laminating several different functional layers (all 76 x 76 mm(2)) including a patterned polyimide layer with a flip-chip bonded CMOS chip, a pressure sensitive acrylic adhesive (PSA) layer with a fluidic cutout, an optically transparent polymethyl methacrylate (PMMA) film, a PSA layer with a via, a patterned polyimide layer with a flip-chip bonded silicon chip, a PSA layer with a fluidic cutout, and a glass cover plate layer. Versatility of the stacked microlaboratory was demonstrated by various automated assays. Escherichia coli bacteria and Alexa-labeled protein toxin staphylococcal enterotoxin B (SEB) were detected by electric-field-driven immunoassays on a single chip with a specific-to-nonspecific signal ratios of 4.2:1 and 3.0:1, respectively. Furthermore, by integrating the microlaboratory with a module for strand displacement amplification (SDA), the identification of the Shiga-like toxin gene (SLT1) from E. coli was accomplished within 2.5 h starting from a dielectrophoretic concentration of intact E. coli bacteria and finishing with an electric-field-driven DNA hybridization assay, detected by fluorescently labeled DNA reporter probes. The integrated microlaboratory can be potentially used in a wide range of applications including detection of bacteria and biowarfare agents, and genetic identification.

Mitogen therapy for biological warfare/terrorist attacks and viral hemorrhagic fever control.

Ken Alibek was for 17 years a leader in Biopreparat, the Soviet Union's top secret agency involved in developing and stockpiling the most lethal bacteria, viruses, and toxins in the history of mankind before he defected with his family to the United States in 1992. Very contrite when he discovered he had been misled to believe that his efforts had been essential to the survival of his homeland, Alibek has become active sounding an alarm about, among other things, thousands of unemployed Russian scientists who have been seeking survival by selling their destructive expertise to rouge states and bioterrorists. Working full time in devising protective measures that might help control the damaging effects of terrorist attacks, Alibek has placed strong emphasis on stimulating nonspecific immunities of victims mainly with interleukins and other cytokines. A more productive alternative would be giving mitogens such as PHA and PWM to reinforce vaccine and antibiotic actions, at the same time stimulating protective immune, myelopoietic, and lymphopoietic responses. A key objective would be to find an effective management for the dreaded viral hemorrhagic fevers. Using Ebola infection as an experimental model, Yang et al. have shown that PHA can block both the viral secretions that inhibit neutrophil immune responses and the viral transmembrane glycoprotein that facilitates damage of the human endothelial cells responsible for the lethal hemorrhagic manifestations. Normal serum glycoproteins have in the past been clearly shown to inhibit the functions of PHA, thereby increasing dosage requirements. Extrapolation of this interaction with serum glycoproteins suggests that PHA given intravenously in adequate dosage should readily be able to block the deleterious Ebola virus glycoprotein effects. Data in an extensive classification of the hemorrhagic fever viruses recently presented by Barry make it possible to predict that mitogen therapy should be effective for virtually all of the disorders included. Therapeutic trials should best start with intravenous administration of PHA since this is the mitogen about which most is known and the only one given to humans, although the nonagglutinating advantages of fraction i.v. of PHA should be evaluated as a replacement. Functioning in a different mode, PWM has the advantage of much greater potency, and can be given either intravenously or orally, since these appear to be equally effective routes of administration. The best means of properly integrating the use of these mitogens needs to be determined.

Legal preparedness for bioterrorism.

Responding to a terrorist biological weapon attack poses new challenges not only for the public health response community but also to the very construct of public health police powers as we know them today. States are debating the merits of revising and updating these powers in order to ensure an effective and legally appropriate response. This article covers three aspects of the policy debate: the experience in one state from a legislative perspective, a discussion from an academic viewpoint, and one example of the role of enhanced powers from the response perspective.

Bioterrorismo: apuntes para una agenda de lo inesperado / Preparedness aginst bioterrorist attacks in Mexico

La vulnerabilidad de las poblaciones humanas a terrorismo químico, biológico, radiológico y nuclear ha sido discutida pero insuficientemente analizada. Las políticas de salud pública carecen de información sólida y relevante para diseñar programas costo-efectivos para prevenir o mitigar este tipo de incidentes en el futuro. Los gobiernos tienen insuficiencia presupuestal para hacer frente a estos ataques. Por lo anterior, en países en desarrollo, como México, es conveniente reflexionar sobre acciones preventivas particulares, los agentes potenciales y prevención de la transmisión. Propuestas. La respuesta internacional ante un ataque biológico debe basarse en acuerdos internacionales que prohiben el uso de agentes biológicos con fines de guerra o defensa; así como intercambio académico y tecnológico para la prevención de ataques bioterroristas. Las recomendaciones, a escala nacional, ante un ataque son: a) una estrategia legal de defensa contra bioterrorismo; b) educación, como clave para defensa contra bioterrorismo; c) creación de un programa nacional de coordinación interinstitucional antibioterrorista, que incluya asistencia de urgencias médicas y la obtención de evidencia médica forense; d) instalación de un sistema de vigilancia epidemiológica ante el uso de armas biológicas; e) instauración de un laboratorio de análisis de material biológico asociado con incidentes terroristas; f) preparación de campañas públicas de información; g) garantía de abasto de material diagnóstico, protección especial y tratamiento de urgencias ante ataques biológicos; h) descentralización de sistemas de alerta para detección oportuna de terrorismo biológico; i) respuesta a acciones bioterroristas dirigidas contra animales y plantas, y j) creación de Comités de Etica ante situaciones de urgencia por un ataque biológico. Conclusiones. El cambiante panorama epidemiológico requiere de una infraestructura suficiente para establecer diagnósticos de enfermedades emergentes o insólitas como sería el caso de una agresión bioterrorista. La tecnología permite identificar, en pocas horas, a múltiples agentes infecciosos por análisis de ácidos nucleicos y debería ser accesible en laboratorios de referencia. Todas las acciones requieren de presupuestos suficientes para enfrentar esta posible eventualidad. La situación es potencialmente de extrema gravedad y así deberá considerarse al cuantificar la inversión. El texto en inglés está disponible en: http://www.insp.mx/salud/index.html

Agentes biológicos y terrorismo. Medidas preventivas y recomendaciones de manejo / Biological agents and terrorism. Preventive measures and management recommendations

Los recientes acontecimientos de infección por ántrax en los Estados Unidos de América, en el contexto de posibles ataques bioterroristas han motivado el reflexionar sobre la gama de organismos biológicos susceptibles de utilizarse como armas en la guerra bioquímica y biológica. Dichos agentes van más allá del bacilo del ántrax e incluyen, entre otros, el virus de la viruela, las bacterias causantes de la peste, el botulismo, la brucelosis y zoonosis como la fiebre aftosa. El presente trabajo está orientado a describir las principales características de dichos problemas y las medidas sanitarias destinadas a su prevención, detección oportuna y tratamiento.

Strategies for the prevention of a successful biological warfare aerosol attack.

Biological warfare (BW) aerosol attacks are different from chemical attacks in that they may provide no warning/all clear signals that allow the soldier to put on or remove his M17/M40 protective mask. Methods are now being perfected to detect a BW aerosol cloud using an airborne (helicopter) pulsed laser system to scan the lower altitudes upwind from a troop concentration of corps size, and to sample and analyze the nature of the aerosol within a brief time interval. This system has certain limitations and vulnerabilities, since it is designed specifically to detect a line-type aerosol attack. Provision of, training with, and field use of a lightweight dust mist or HEPA filter respirator for each soldier is proposed for protection against undetected aerosol attacks. This particulate filter respirator would be issued in addition to the M17/M40 mask. Such a BW respirator will be able to purify the soldier's air by removing particles in the 0.3- to 15-micro m-diameter range with an efficiency of 98 to 100%. Particle size of BW aerosols is in the same range, with an optimum size for high-efficiency casualty production of 1 to 5 micro m mass median diameter. The proposed BW respirator will be lightweight; will require low inhalation pressures; will be comfortable to wear for prolonged periods; will not interfere with vision, hearing, and communication; and will not degrade overall effectiveness and performance to the degree observed with the M17/M40 masks. Such respirators would be worn as part of a contingency defense against an enemy likely to use BW agents. This respirator could be worn for prolonged periods when under threat of an undetectable BW attack during weather conditions favorable to the success of such an attack (i.e., low wind velocity and temperature inversion in the target area). In addition, tactically important assets such as command and control centers and missile batteries can also be protected continuously by air filtration systems powered by electricity (modular collective protection equipment). Vaccinations against anthrax, botulism, Q fever, plague, and tularemia are now available and immune protection against ricin and staphylococcal toxins appears feasible in the near future. Chemotherapy can also be provided for prophylaxis of infectious agents released on the battlefield. The vaccines and antibiotics can provide back-up protection against an unexpected BW attack during a period when the BW respirator is not in use or malfunctions due to a poor seal or filter leak. Enemy sites of biological weapon production, assembly, testing, and storage, and delivery vehicles can be targeted for destruction by bombs and/or missiles. An integrated, well-planned, BW defense with multiple components can decrease the likelihood of a successful enemy BW aerosol attack.