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At least 1,531 records · Page 85Linked to original sources

PubMed2005

Expression of an anti-botulinum toxin A neutralizing single-chain Fv recombinant antibody in transgenic tobacco.

Botulinum neurotoxins (BoNTs) are the most poisonous substances known and are thus classified as high-risk threats for use as bioterror agents. To examine the potential of transgenic plants as bioreactors for the production of BoNT antidotes, we transformed tobacco with an optimized, synthetic gene encoding a botulinum neurotoxin A (BoNT/A) neutralizing single-chain Fv (scFv) recombinant antibody fragment. In vitro mouse muscle twitch assays demonstrated the functional utility of this scFv extracted from tobacco for neutralizing the paralytic effects of BoNT/A at neuromuscular junctions. Based on the efficiency of the scFv capture process and the dose required to antidote a human being, 1-2 ha of this tobacco could yield up to 4 kg of scFv, which would be enough to contribute to the manufacture of 1,000,000 therapeutic doses of a monoclonal antibody (mAb) cocktail capable of neutralizing the effects of BoNT poisoning. Transgenic plants could provide an inexpensive production platform for expression of multiple mAbs toward the creation of polyclonal therapies (i.e. pooled mAbs) as the next improvement in recombinant antibody therapy.

Botulinum Toxins, Type A↗

PubMed2006

Immune responses elicited by bacterial minicells capable of simultaneous DNA and protein antigen delivery.

Recent events surrounding emerging infectious diseases, bioterrorism and increasing multidrug antibiotic resistance in bacteria have drastically increased current needs for effective vaccines. Many years of study have shown that live, attenuated pathogens are often more effective at delivering heterologous protein or DNA to induce protective immune responses. However, these vaccine carriers have inherent safety concerns that have limited their development and their use in many patient populations. Studies using nonliving delivery mechanisms have shown that providing both protein antigen and DNA encoding the antigen to an individual induces an improved, more protective immune response but rarely, if ever, are both delivered simultaneously. Here, non-replicating bacterial minicells derived from a commensal E. coli strain are shown to effectively induce antigen-specific immune responses after simultaneous protein and DNA delivery. These data demonstrate the potential use of achromosomal bacterial minicells as a vaccine carrier.

Administration, Intranasal↗

PubMed2006

Epidemic and pandemic influenza, who cares and how?

The 2005 hurricanes, Katrina and Rita, demonstrated that Mother Nature remains a bigger threat to mankind than bioterrorism or even terrorism. This is no less the case in the expected influenza pandemic that could infect up to 1 billion people worldwide killing millions and disrupting the supply of essential services and provoking social disruption. With influenza however, mankind does have the opportunity to make necessary preparations for the threat of a pandemic that could break out tomorrow, next year or within the next decade. Indeed, the events in New Orleans have sent "a strong message that knowledge is not enough, everyone predicted it [referring to hurricane Katrina], but no one did much about it--you need a detailed plan to deal with these threats," explained Dr. J.S. Oxford to the conference seminar on "epidemic and pandemic influenza, who cares and how?" During this session, participants discussed the state of pandemic preparedness listening to representatives from the UK and Canada who presented overviews of their preparedness plans, viewed as among the best examples of current practice and to a study on compliance with the WHO guidelines on flu vaccination.

Antiviral Agents↗

PubMed2004

Concentrating, purifying and detecting waterborne parasites.

There has been recent emphasis on developing better methods for detecting diseases of zoonotic and veterinary importance. This has been prompted by an increase in human disease agents detectable in environmental samples, the potential for bioterrorism, and the lowering of international trade barriers and expansion of personal travel, which are bringing previously considered exotic diseases to new geographical localities. To appreciate the complexities of developing detection methods and working with environmental samples, it is appropriate to review technologies currently in use, as well as those in development and presently limited to research laboratories. Discussion of parasite detection would not be possible without including methods for parasite sampling, concentration, and purification because it is often necessary to process large sample volumes prior to analysis, and no reliable methods are available for significantly amplifying parasites in vitro. Reviewing proven methods currently in use will provide a baseline for generating, accepting and implementing the more sensitive and specific methods under development today.

Animals↗

PubMed2003

New insights into the evolutionary relationships between arenaviruses provided by comparative analysis of small and large segment sequences.

Arenaviruses are rodent-borne negative-stranded bisegmented RNA viruses. Five arenaviruses are etiologic agents of hemorrhagic fever in humans and are potential agents of bioterrorism. They are classified as Biosafety level 4 agents and listed in the category A of the Pathogen Agents edited by the Center for Disease Control and Prevention. To date, evolution and phylogeny of arenaviruses have been based on the analysis of sequences derived from structural genes (small RNA segment) exclusively, due to the lack of sequences available for the large RNA segment. In this study, partial sequences of the polymerase gene were determined for 18 species of arenaviruses and used to investigate phylogenetic relationships. Comparative analysis of topologies obtained from polymerase and structural gene analyses permitted us to determine the evolutionary origin of the major parent of the North American recombinant arenaviruses, and to investigate the role of genetic exchange (reassortment and recombination) in the evolutionary mechanisms driving the evolution of the genus Arenavirus.

Arenaviruses, New World↗

PubMed2006

B5-deficient vaccinia virus as a vaccine vector for the expression of a foreign antigen in vaccinia immune animals.

Recombinant vaccinia viruses have shown promise as vaccine vectors. However, their effectiveness is markedly reduced by pre-existing anti-vaccinia immunity. The possibility of new vaccinia immunizations in the event of a bioterror-related smallpox release poses an additional negative impact on the utility of vaccinia-based vectors. Thus, we aimed to design a vaccinia vector that would enhance the immune response to an expressed foreign protein in a pre-immune animal model. To do this, we made use of the finding that most neutralizing antibodies against the extracellular form of vaccinia virus are directed against the B5 protein. We found that mice immunized with vaccinia, primed with Gag plasmid DNA, and boosted with a recombinant vaccinia virus lacking the majority of the B5 ectodomain expressing a test antigen, HIV Gag, had stronger anti-Gag immune responses than mice that were boosted with a wild-type virus-expressing Gag. These findings are particularly striking given the more attenuated phenotype of this virus, as compared to its wild-type counterpart. Importantly, we found that vaccination with a B5R deletion virus, followed by boosting with the Gag-expressing virus lacking the majority of the B5 ectodomain, resulted in poorer anti-Gag immune responses. Thus, recombinant vaccinia viruses lacking the B5 ectodomain may serve as vaccine vectors in DNA prime-vaccinia boost vaccinations of individuals with pre-existing immunity against vaccinia. These data open the possibility of extending the potential benefit of replication competent recombinant vaccinia virus vectors to a larger population.

AIDS Vaccines↗

PubMed2005

Arenavirus extinction through lethal mutagenesis.

Viral hemorrhagic fevers represent serious human public health problems causing devastating and often lethal disease. Several hemorrhagic fevers are caused by arenaviruses including Lassa fever virus (LFV) and the South American viral hemorrhagic fevers (SAHF). In recent years, increased air travel between Africa and other areas has led to the importation of LFV into the US, Europe, Japan, and Canada. This has raised awareness about arenaviruses as potential emerging viruses. Moreover, because of its severe morbidity and high mortality, and transmissibility from human to human, weaponized forms of LFV poses a real threat as agent of bioterrorism. No licensed vaccine is available in the US, and currently there is not efficacious therapy to treat these infections. Therefore, the importance of developing novel effective antiviral drugs to combat HF arenaviruses, for which the prototypic Arenavirus lymphocytic choriomeningitis virus (LCMV) provides us with an excellent model system. Recent findings have shown that LCMV multiplication both in cultured cells and in vivo is highly susceptible to the mutagenic agent 5-fluorouracil (FU). FU-mediated extinction of LCMV was associated with only modest increases in virus mutation frequencies, but did not significantly affect virus replication and transcription, or virus particle formation. These findings indicate that, as with other riboviruses, lethal mutagenesis is effective also against LCMV raising the possibility of using this novel antiviral strategy to combat pathogenic arenaviruses.

Animals↗

PubMed2002

The in vitro and in vivo protective activity of monoclonal antibodies directed against Hantaan virus: potential application for immunotherapy and passive immunization.

Hantaan virus (HTNV), a member of the genus Hantavirus, family Bunyaviridae, is an etiologic agent causing a serious human disease, hemorrhagic fever with renal syndrome (HFRS), with a mortality as high as 15% and is also a potential bioterrorism agent. It is urgently needed to develop anti-HTNV-neutralizing monoclonal antibodies (MAbs) for treatment and prevention of HTNV infection. In the present study, 18 murine MAbs directed against HTNV strain Chen were generated and characterized. Among these MAbs, 13 were directed against viral nucleocapsid protein (NP), four recognized the viral envelope glycoprotein G2 and one reacted with both NP and G2. Only those MAbs that recognize the epitopes on G2 were positive in hemagglutination inhibition (HI) test and had in vitro virus-neutralizing activity and in vivo protective activity against HTNV infection of susceptible mice. Since all the mice were protected by administration of the virus-neutralizing MAbs one day before and two days after HTNV challenge, these neutralizing MAbs are potentially useful for pre- and post-exposure prophylaxis and for immunotherapy of HTNV infection. Phase II clinical trials of these neutralizing MAbs for emergent treatment of patients with HTNV infection in early stages of HRFS are carried out in endemic areas in China.

Animals↗

PubMed2000

Biological terrorism: understanding the threat, preparation, and medical response.

The thought of an outbreak of disease caused by the intentional release of a pathogen or toxin in an American city was alien just 10 years ago. Many people believed that biological warfare was only in the military's imagination, perhaps to be faced by soldiers on a far-away battlefield, if at all. Political factors--and possibly biotechnology--have changed that. As we enter the new millennium, national, state, and local governments in the United States are preparing for what is now called "not if, but when" biological terrorism. In contrast to the acute onset and first-responder focus with a chemical attack, in a bioterrorist attack, the physician and the hospital will be at the center of the fray. Whether the attack is a hoax, a small food-borne outbreak, a lethal aerosol cloud moving silently through a city at night, or the introduction of contagious disease, the physician who understands threat agent characteristics and diagnostic and treatment options and who thinks like an epidemiologist will have the greatest success in limiting the impact of the attack. As individual health-care providers, we must add the exotic agents to our diagnostic differentials. Hospital administrators must consider augmenting diagnostic capabilities and surveillance programs and even making infrastructure modifications in preparation for the treatment of victims of bioterrorism. Above all, we must all educate ourselves. If done correctly, preparation for a biological attack will be as "dual use" as the facility that produced the weapon. A sound public health infrastructure, which includes all of us and our resources, will serve this nation well for the control of disease, no matter what the cause of the disease.

Biological Warfare↗

PubMed2003

Eosinophilic-lymphocytic myocarditis after smallpox vaccination.

Smallpox is an eradicated viral disease that has re-emerged as a potential bioterrorism threat. Smallpox vaccination was historically the most effective defence measure against wild smallpox virus. The risk of myopericarditis after vaccination might limit this option. We report a case of biopsy-proven eosinophilic-lymphocytic myocarditis diagnosed in vivo with histological evidence for eosinophil-mediated cardiac myocyte necrosis shortly after smallpox vaccination. Furthermore, we report a beneficial haemodynamic response to high-dose corticosteroids. A better understanding of the aberrant immune mechanism of myocyte injury after smallpox vaccination might improve the risk/benefit assessment for people considering smallpox vaccination and better smallpox vaccines in the future.

Adult↗

PubMed2003

Poxviruses as vaccine vectors.

The discovery of Jenner in 1798 founded the science of immunology and eventually led to smallpox eradication from the earth in 1980 after a world-wide vaccination campaign with vaccinia virus (another poxvirus) and paradoxically, despite the eradication of smallpox, there has been an explosion of interest in vaccinia virus in the eighties. This interest has stemmed in part from the application of molecular genetics to clone and express foreign genes from recombinant vaccinia viruses. Vaccinia is also gaining renewed interest due to bioterrorism. These recombinant viruses have multiple applications in research and vaccinology and led to the development of vectored vaccines, such as the recombinant vaccinia rabies vaccine used to eliminate rabies in Western Europe and, more recently, in the United States. Secondly, alternative poxvirus vectors, such as avipox viruses, were proved to be even safer and efficacious non-replicating vectors (suiciole vectors) when used in non-avian species.

Animals↗

PubMed2003

A real-time PCR assay for the detection of varicella-zoster virus DNA and differentiation of vaccine, wild-type and control strains.

Varicella-zoster vaccine is a live attenuated virus. It is, therefore, necessary to have a test to differentiate vaccine from wild-type varicella-zoster virus (VZV) strains for the investigation of varicella or zoster-like rash illness in individuals vaccinated previously. In addition, it is necessary to have a rapid VZV assay for use in the context of smallpox bioterrorism laboratory testing. Using specific primers and hybridization probes, a rapid method to differentiate vaccine strain VZV from wild-type VZV was developed based on the presence or absence of a Pst I restriction site within open reading frame (ORF) 38. Using this ORF 38 assay in conjunction with a similar previously described ORF 62 assay allows for further differentiation of vaccine strain, wild-type and a laboratory control strain (Ellen) VZV. This is accomplished because Ellen VZV is similar to wild-type VZV with respect to the ORF 38 assay but is similar to vaccine strain VZV with respect to the ORF 62 assay. The hybridization probes for each ORF are labeled with different fluorescent tags thus allowing both assays to be run simultaneously in a single tube. Both assays demonstrate a high degree of specificity for VZV and can reliably detect between 10 and 100 copies of VZV DNA. Thus, the real-time polymerase chain reaction (PCR) assay for VZV described below provides a rapid assay allowing the simultaneous differentiation of vaccine, wild-type and laboratory control strains of VZV.

Chickenpox↗

PubMed2003

In vitro activity of potential anti-poxvirus agents.

The potential use of variola or another orthopoxvirus such as monkeypox as a weapon of bioterrorism has stimulated efforts to develop new drugs for treatment of smallpox or other poxvirus infections. At the present time only cidofovir is approved for use in the emergency treatment of smallpox outbreaks. Although cidofovir is very active against the orthopoxviruses in vitro and in animal model infections, it is not active when given orally and must be administered with precaution so as to avoid renal toxicity. In an attempt to identify alternative treatment modalities for these infections we have determined the anti-poxvirus activity in vitro of most of the approved antiviral agents as well as a number of cidofovir analogs and prodrugs. From these studies, we have identified the nucleotide analog, adefovir dipivoxil, some alkoxyalkyl esters of cidofovir and a number of prodrugs of cidofovir that warrant further investigation as potential therapies for smallpox or other orthopoxvirus infections.

Adenine↗

PubMed2000

Adventures with poxviruses of vertebrates.

Because they were the largest of all viruses and could be visualised with a light microscope, the poxviruses were the first viruses to be intensively studied in the laboratory. It was clear from an early date that they caused important diseases of humans and their domestic animals, such as smallpox, cowpox, camelpox, sheeppox, fowlpox and goatpox. This essay recounts some of the early history of their recognition and classification and then expands on aspects of research on poxviruses in which the author has been involved. Studies on the best-known genus, Orthopoxvirus, relate to the use of infectious ectromelia of mice as a model for smallpox, embracing both experimental epidemiology and pathogenesis, studies on the genetics of vaccinia virus and the problem of non-genetic reactivation (previously termed 'transformation') and the campaign for the global eradication of smallpox. The other group of poxviruses described here, the genus Leporipoxvirus, came to prominence when the myxoma virus was used for the biological control of Australian wild rabbits. This provided a unique natural experiment on the coevolution of a virus and its host. Future research will include further studies of the many immunomodulatory genes found in all poxviruses of vertebrates, since these provide clues about the workings of the immune system and how viruses have evolved to evade it. Some of the many recombinant poxvirus constructs currently being studied may come into use as vaccines or for immunocontraception. A field that warrants study but will probably remain neglected is the natural history of skunkpox, raccoonpox, taterapox, yabapox, tanapox and other little-known poxviruses. A dismal prospect is the possible use of smallpox virus for bioterrorism.

Animals↗

PubMed2001

Telehealth and the global health network in the 21st century. From homecare to public health informatics.

The Information Era we live in has created new challenges and opportunities. This age of information highways has an economic price, which has not been properly evaluated. Detailed studies are needed to prove the cost and medical effectiveness of these technologies as well as its effects in the quality of life. Our society's future may depend on it. People are living longer, discoveries in genetics and in information technology are not only helping produce newer drugs faster but also providing the opportunity to exploit new areas such as disease prevention. These technologies provide a variety of opportunities to address public health challenges such as universal access for the uneducated, counter-bioterrorism, telemedicine, distance education, and home care. These opportunities present new challenges such as: surveillance, privacy/confidentiality/security of personal information which will affect all of our lives. No strategy has been presented publicly (yet) addressing (neither) the benefits (n)or the pitfalls of such technologies. From an economic point of view it is an imperative necessity to understand the importance of the Information Technology Infrastructure (ITI) and what it is. The investments in creating and maintaining this ITI will not come from a single application area such as healthcare, but rather from a combination of sources such as electronic commerce, banking, financial, manufacturing, entertainment, travelling, weather forecasting, pharmaceuticals, education, defence and many other 'industries' or application areas.

Aged↗

PubMed2004

Oral pemphigus vulgaris after anthrax vaccine administration: association or coincidence?

Pemphigus vulgaris is an autoimmune blistering disorder of the skin and mucous membranes. Numerous medications, ultraviolet light, and radiation have all been implicated in the etiology of the disease. We present a patient with pemphigus vulgaris whose disease developed after administration of anthrax vaccine. The histologic and immunofluorescence findings were characteristic of pemphigus vulgaris. Adverse systemic events associated with the anthrax vaccine consist primarily of flu-like symptoms. Previous cases of pemphigus vulgaris associated with anthrax vaccine administration have not been reported. Considering the recent deliberate outbreaks of anthrax and continued threats of bioterrorism, the potential exists for widespread administration of the anthrax vaccine. Accordingly, continued observation and documentation of true adverse events is needed.

Adult↗

PubMed1999

Emergency physicians and biological terrorism.

Recent developments, such as the bombings of the World Trade Center in 1993 and the Alfred P. Murrah Federal Building in Oklahoma City in 1995, the sarin attacks in Tokyo and Matsumoto, Japan, and US Embassy bombings in Kenya and Tanzania in 1998, have heightened fears of terrorist attacks. Future terrorist activities will continue to involve bombs and firearms, but may also include weapons of mass destruction, including biological agents. Recent US government initiatives have recognized the threats to our country from these weapons and have funded planning and response programs. These preparedness programs are being built on existing infrastructure of EMS and fire services' plans for hazardous materials response. Appropriate emergency department and hospital response, guided by public health principles, could significantly limit the morbidity and mortality of biological warfare agents. Inappropriate response by the medical community may worsen a chaotic and potentially devastating situation. This article discusses planning and response issues central to a potential bioterrorism event.

Biological Warfare↗

PubMed2000

Anthrax threats: a report of two incidents from Salt Lake City.

The threat of anthrax as an agent of bioterrorism in the U.S. is very real, with 47 incidents of possible exposure involving 5664 persons documented by the Federal Bureau of Investigation over a 14-month period in 1998 and 1999. The highly visible and potentially devastating effects of these threats require a well-coordinated and well-organized Emergency Medical Services (EMS) and Emergency Department (ED) response to minimize panic and reduce the potential spread of an active and deadly biologic agent. This requires planning and education before the event. We describe the events of two anthrax threats in a major metropolitan area. The appropriate EMS and ED response to these threats is outlined.

Adult↗