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Showing papers on "Anthrax vaccines published in 2004"


Journal ArticleDOI
02 Jan 2004-Vaccine
TL;DR: Results suggested that the antibody response, as determined by the quantitative anti-rPA IgG ELISA and toxin neutralizing antibody (TNA) assay, were significant predictors of protection against a B. anthracis aerosol spore challenge in rabbits.

168 citations


Journal ArticleDOI
TL;DR: Preclinical evaluation of this cationic lipid-formulated bivalent PA and LF vaccine is complete, and the vaccine has received U.S. Food and Drug Administration Investigational New Drug allowance.
Abstract: DNA vaccines provide an attractive technology platform against bioterrorism agents due to their safety record in humans and ease of construction, testing, and manufacture. We have designed monovalent and bivalent anthrax plasmid DNA (pDNA) vaccines encoding genetically detoxified protective antigen (PA) and lethal factor (LF) proteins and tested their immunogenicity and ability to protect rabbits from an aerosolized inhalation spore challenge. Immune responses after two or three injections of cationic lipid-formulated PA, PA plus LF, or LF pDNAs were at least equivalent to two doses of anthrax vaccine adsorbed (AVA). High titers of anti-PA, anti-LF, and neutralizing antibody to lethal toxin (Letx) were achieved in all rabbits. Eight or nine animals in each group were challenged with 100× LD50 of aerosolized anthrax spores 5 or 9 weeks after vaccination. An additional 10 animals vaccinated with PA pDNA were challenged >7 months postvaccination. All animals receiving PA or PA plus LF pDNA vaccines were protected. In addition, 5 of 9 animals receiving LF pDNA survived, and the time to death was significantly delayed in the others. Groups receiving three immunizations with PA or PA plus LF pDNA showed no increase in anti-PA, anti-LF, or Letx neutralizing antibody titers postchallenge, suggesting little or no spore germination. In contrast, titer increases were seen in AVA animals, and in surviving animals vaccinated with LF pDNA alone. Preclinical evaluation of this cationic lipid-formulated bivalent PA and LF vaccine is complete, and the vaccine has received U.S. Food and Drug Administration Investigational New Drug allowance.

119 citations


Journal ArticleDOI
TL;DR: This in vitro assay measures the functional ability of antisera, containing antibodies to anthrax lethal toxin, to specifically protect J774A.1 cells against Bacillus anthracis lethal toxin cytotoxicity.

88 citations


Journal ArticleDOI
TL;DR: The utility of ClyA for enhancing the immunogenicity of an otherwise problematic antigen was demonstrated by engineering ClyA fused to the domain 4 (D4) moiety of Bacillus anthracis protective antigen (PA) and the induction of PA-specific gamma interferon and interleukin 5 responses was observed in splenocytes.
Abstract: Bacterial live-vector vaccines aim to deliver foreign antigens to the immune system and induce protective immune responses, and surface-expressed or secreted antigens are generally more immunogenic than cytoplasmic constructs. We hypothesize that an optimum expression system will use an endogenous export system to avoid the need for large amounts of heterologous DNA encoding additional proteins. Here we describe the cryptic chromosomally encoded 34-kDa cytolysin A hemolysin of Salmonella enterica serovar Typhi (ClyA) as a novel export system for the expression of heterologous antigens in the supernatant of attenuated Salmonella serovar Typhi live-vector vaccine strains. We constructed a genetic fusion of ClyA to the reporter green fluorescent protein and showed that in Salmonella serovar Typhi CVD 908-htrA, the fusion protein retains biological activity in both domains and is exported into the supernatant of an exponentially growing live vector in the absence of detectable bacterial lysis. The utility of ClyA for enhancing the immunogenicity of an otherwise problematic antigen was demonstrated by engineering ClyA fused to the domain 4 (D4) moiety of Bacillus anthracis protective antigen (PA). A total of 11 of 15 mice immunized intranasally with Salmonella serovar Typhi exporting the protein fusion manifested fourfold or greater rises in serum anti-PA immunoglobulin G, compared with only 1 of 16 mice immunized with the live vector expressing cytoplasmic D4 (P = 0.0002). In addition, the induction of PA-specific gamma interferon and interleukin 5 responses was observed in splenocytes. This technology offers exceptional versatility for enhancing the immunogenicity of bacterial live-vector vaccines.

78 citations


Journal ArticleDOI
TL;DR: A formulated, pressure-sensitive, dry adhesive patch, which is stable and can be manufactured in large scale, elicited comparable immunoglobulin G and TNA responses, suggesting that an anthrax vaccine patch is feasible and should advance into clinical evaluation.
Abstract: Background. Transcutaneous immunization (TCI) is a needle-free technique that delivers antigens and adjuvants to potent epidermal immune cells. To address critical unmet needs in biodefense against anthrax, we have designed a novel vaccine delivery system using a dry adhesive patch that simplifies administration and improves tolerability of a subunit anthrax vaccine. Methods. Mice and rabbits were vaccinated with recombinant protective antigen of Bacillus anthracis and the heat-labile toxin of Escherichia coli. Serologic changes, levels of toxin-neutralizing antibodies (TNAs), and pulmonary and nodal responses were monitored in the mice. A lethal aerosolized B. anthracis challenge model was used in A/J mice, to demonstrate efficacy. Results. The level of systemic immunity and protection induced by TCI was comparable to that induced by intramuscular vaccination, and peak immunity could be achieved with only 2 doses. The addition of adjuvant in the patch induced superior TNA levels, compared with injected vaccination. Conclusions. Anthrax vaccine patches stimulated robust and functional immune responses that protected against lethal challenge. Demonstration of responses in the lung suggests that a mechanism exists for protection against challenge with aerosolized anthrax spores. A formulated, pressure-sensitive, dry adhesive patch, which is stable and can be manufactured in large scale, elicited comparable immunoglobulin G and TNA responses, suggesting that an anthrax vaccine patch is feasible and should advance into clinical evaluation.

73 citations


Journal ArticleDOI
TL;DR: The efficacy and immunogenicity of human anthrax vaccines in well-defined animal models are reviewed and the progress toward developing a rugged immunologic correlate of protection is reviewed.
Abstract: The intentional use of Bacillus anthracis, the etiological agent of anthrax, as a bioterrorist weapon in late 2001 made our society acutely aware of the importance of developing, testing, and stockpiling adequate countermeasures against biological attacks. Biodefense vaccines are an important component of our arsenal to be used during a biological attack. However, most of the agents considered significant threats either have been eradicated or rarely infect humans alive today. As such, vaccine efficacy cannot be determined in human clinical trials but must be extrapolated from experimental animal models. This article reviews the efficacy and immunogenicity of human anthrax vaccines in well-defined animal models and the progress toward developing a rugged immunologic correlate of protection. The ongoing evaluation of human anthrax vaccines will be dependent on animal efficacy data in the absence of human efficacy data for licensure by the U.S. Food and Drug Administration.

72 citations


Journal ArticleDOI
TL;DR: The practical implications from the studies reported herein are that the protective capacity of memory depends on the PA dose used for the primary immunization and that the effectiveness of booster immunizations for the postexposure treatment of anthrax may be very limited when no detectable antibodies are present in primed animals prior to Bacillus anthracis spore exposure.
Abstract: Protective antigen (PA)-based vaccination is an effective countermeasure to anthrax infection. While neutralizing anti-PA antibody titers elicited by this vaccine serve as good correlates for protection against anthrax (S. Reuveny, M. D. White, Y. Y. Adar, Y. Kafri, Z. Altboum, Y. Gozes, D. Kobiler, A. Shafferman, and B. Velan, Infect. Immun. 69:2888-2893, 2001), no data are available on the contribution of the immunological memory for PA itself to protection. We therefore developed a guinea pig model in which a primary immunization with threshold levels of PA can induce a long-term T-cell immunological memory response without inducing detectable anti-PA antibodies. A revaccination of primed animals with the same threshold PA levels was effective for memory activation, yielding a robust and rapid secondary response. A challenge with a lethal dose (40 50% lethal doses; 2,000 spores) of spores after the booster vaccinations indicated that animals were not protected at days 2, 4, and 6 postboosting. Protection was achieved only from the 8th day postboosting, concomitant with the detection of protective levels of neutralizing antibody titers in the circulation. The practical implications from the studies reported herein are that, as expected, the protective capacity of memory depends on the PA dose used for the primary immunization and that the effectiveness of booster immunizations for the postexposure treatment of anthrax may be very limited when no detectable antibodies are present in primed animals prior to Bacillus anthracis spore exposure. Therefore, to allow for the establishment of memory-dependent protection prior to the expected onset of disease, booster immunizations should not be used without concomitant antimicrobial treatment in postexposure scenarios.

65 citations


Journal ArticleDOI
TL;DR: Three immunizations of mice with recombinant protective antigen by transcutaneous immunization induced long-term neutralizing antibody titers that were superior to those obtained with aluminum-adsorbed rPA, and 100% protection was observed against lethal anthrax challenge.
Abstract: Three immunizations of mice with recombinant protective antigen (rPA) by transcutaneous immunization (TCI) induced long-term neutralizing antibody titers that were superior to those obtained with aluminum-adsorbed rPA. In addition, rPA alone exhibited adjuvant activity for TCI. Forty-six weeks after completion of TCI, 100% protection was observed against lethal anthrax challenge.

58 citations


Journal ArticleDOI
22 Oct 2004-Vaccine
TL;DR: The results demonstrate that, as expected, the major antigen present in the vaccine is PA, and the 83 and 63 kDa species are dominant but there are numerous lower molecular weight fragments resulting from proteolytic cleavage.

56 citations


Journal ArticleDOI
TL;DR: In this article, the authors extracted membranal proteins from a stationary-phase culture of a nonvirulent B. anthracis strain, devoid of the native virulence plasmids pXO1 and pX02, were separated by two-dimensional electrophoresis (2-DE) and a characteristic protein map was defined.
Abstract: Bacillus anthracis is the causative agent of anthrax disease. Improvement of existing anthrax vaccines, which are currently based on the administration of Protective Antigen (the highly immunogenic nontoxic subunit of the bacterial toxin) may entail other bacterial immunogenic elements, part of which are predicted to reside on the surface of bacterial cells. In the present study, membranal proteins extracted from a stationary-phase culture of a nonvirulent B. anthracis strain, devoid of the native virulence plasmids pXO1 and pX02, were separated by two-dimensional electrophoresis (2-DE) and a characteristic protein map was defined. The proteomic analysis allowed matrix-assisted laser desorption/ionizatlon-time of flight mass spectrometry-assisted identification of 86 protein spots which represent the product of 30 individual open reading frames (ORF). Among these, a prevalent class of proteins was the S-layer proteins (which were found to represent more than 75% of the B. anthracis membranal fraction) and proteins containing S-layer homology (SLH)-membranal localization domains. Five novel SLH proteins, previously inferred only from bioinformatic ORF analysis (draft genome sequence), were identified and one was shown to be a highly abundant membranal protein. Western blots of the 2-DE gels were probed with sera from convalescent rabbits and guinea pigs infected with virulent B. anthracis (Vollum strain). This analysis revealed that B. anthracis immune animals exhibit antibodies against at least 14 distinct membranal proteins present in the 2-DE map, establishing that these proteins are expressed in vivo and are able to elicit an immune response. The identification of the protein components of the B. anthracis membranal fraction, as well as the establishment of their potential immunogenicity, underscore the strength of the proteomic approach for identifying molecules which may serve for further analysis of immune and protective abilities.

53 citations


Journal ArticleDOI
TL;DR: It is shown that antibodies reactive with the B. anthracis capsule can be elicited in mice by immunization with a conjugate consisting of a synthetic gamma-D-glutamic acid nonamer peptide covalently coupled to keyhole limpet hemocyanin, and suggest that anti-capsular antibodies could mediate the clearance of vegetative B. Anthracis cells in vivo.
Abstract: The capsule of Bacillus anthracis, a polymer of Q-D-glutamic acid, functions as a virulence determinant and is a poor immunogen. In this study we show that antibodies reactive with the B.anthracis capsule can be elicited in mice by immunization with a conjugate consisting of a synthetic Q-D-glutamic acid nonamer peptide (Q-D-glu9) covalently coupled to keyhole limpet hemocyanin. The serum response to Q-Dglu9 was comprised primarily of IgG antibodies that recognized an epitope requiring a minimum of four Q-linked D-glutamic acid residues. Antibodies to (Q-D-glu9) bound to the surface of encapsulated B.anthracis cells and mediated opsonophagoctosis. These findings suggest that anti-capsular antibodies could mediate the clearance of vegetative B.anthracis cells in vivo. Thus, inclusion of an immunogenic capsular component as well as protective antigen in new anthrax vaccines would generate immune responses targeting both the bacteremic and toxigenic aspects of anthrax infection and thus may increase protective efficacy.

Journal ArticleDOI
TL;DR: The anthrax bipartite lethal toxin (protective antigen (PA) and lethal factor (LF))-specific antibody responses of humans receiving the UK licensed anthrax vaccine were determined and vaccinated individuals recognized the same PA epitope as the protective mouse lethal toxin neutralizing monoclonal 2D3 suggesting that this may also be a target for human protection.
Abstract: The anthrax bipartite lethal toxin (protective antigen (PA) and lethal factor (LF))-specific antibody responses of humans receiving the UK licensed anthrax vaccine were determined. The PA-specific IgG response peaked two weeks post immunization and fell back to pre-boost levels by week 12. The heterogeneity of the host population modulated the extent of the PA-specific antibody response. Significantly lower levels of LF-specific antibodies were also detected. Vaccinated individuals recognized the same PA epitope as the protective mouse lethal toxin neutralizing monoclonal 2D3 suggesting that this may also be a target for human protection.

Journal ArticleDOI
TL;DR: The extent of a reporting bias should be carefully considered when one evaluates the health consequences of anthrax vaccination based on self-reported data.

Journal ArticleDOI
29 Jul 2004-Vaccine
TL;DR: It is found that the serological response of female A/J mice, as measured by a quantitative anti-rPA IgG ELISA, may be an effective method to monitor a manufacturer's consistency for rPA-based vaccines.

Journal ArticleDOI
TL;DR: It appears that the sampling/decontamination workers of the present study either had insufficient exposure to Ba spores to cause the production of anti-PA IgG antibodies or they were exposed to anthrax spores without producing antibody.
Abstract: Aims: To evaluate potential exposure to Bacillis anthracis ( Ba ) spores in sampling/decontamination workers in the aftermath of an anthrax terror attack. Methods: Fifty six serum samples were obtained from workers involved in environmental sampling for Ba spores at the American Media, Inc. (AMI) building in Boca Raton, FL after the anthrax attack there in October 2001. Nineteen sera were drawn from individuals both pre-entry and several weeks after entrance into the building. Nine sera each were drawn from unique individuals at the pre-entry and follow up blood draws. Thirteen donor control sera were also evaluated. Individuals were surveyed for Ba exposure by measurement of serum Ba anti-protective antigen (PA) specific IgG antibodies using a newly developed fluorescent covalent microsphere immunoassay (FCMIA). Results: Four sera gave positive anti-PA IgG results (defined as anti-PA IgG concentrations ⩾ the mean μg/ml anti-PA IgG from donor control sera (n = 13 plus 2 SD which were also inhibited ⩾ 85% when the serum was pre-adsorbed with PA). The positive sera were the pre-entry and follow up samples of two workers who had received their last dose of anthrax vaccine in 2000. Conclusion: It appears that the sampling/decontamination workers of the present study either had insufficient exposure to Ba spores to cause the production of anti-PA IgG antibodies or they were exposed to anthrax spores without producing antibody. The FCMIA appears to be a fast, sensitive, accurate, and precise method for the measurement of anti-PA IgG antibodies.

Journal ArticleDOI
TL;DR: The objective of this work was to study the performance of an anti-PA-ELISA designed to assess the antibody response to anthrax vaccines in mice, and it is believed that assay specificity and the above characteristics are adequate to allow this ELISA to be considered for use in a mouse immunogenicity (potency) test of Anthrax vaccines, and for the standardization of reagents.

Journal Article
TL;DR: The current anthrax vaccine may be acceptable in military populations in impending threat of anthrax exposure, the cost-benefits of vaccination in less high risk military populations may be more questionable and Civilian anthrax vaccination will require a less reactogenic vaccine.
Abstract: Background/aims The Institute of Medicine (IOM) of the United States Academy of Sciences in 2000 encouraged the evaluation of active long-term monitoring studies of large populations to further evaluate the relative safety of anthrax vaccine. Anthrax is a deadly bacterial infectious disease that currently has been engineered as a biological warfare agent. The vaccine produced against anthrax is a cell-free crude culture of the various toxin components of the natural disease. The U.S. military current goal is to vaccinate its entire personnel by 2003. The purpose of this study was to evaluate anthrax vaccination and its association with arthritic, immunological and gastrointestinal adverse reactions based upon analysis of the Vaccine Adverse Events Reporting System (VAERS) database. Methodology We analyzed the VAERS database from 15 December 1997 to 12 April 2000. We also compared the incidence of anthrax adverse reactions with the incidence of adverse reactions reported to VAERS after adult tetanus vaccination. Results Anthrax vaccine was one of the most reactogenic vaccines included in VAERS. The incidence of adverse reactions reported following anthrax vaccine was higher for every reaction analyzed in comparison to the adult vaccine control groups. Conclusions The current anthrax vaccine may be acceptable in military populations in impending threat of anthrax exposure, the cost-benefits of vaccination in less high risk military populations may be more questionable. Civilian anthrax vaccination will require a less reactogenic vaccine. Civilian doctors should be aware of anthrax vaccine adverse reactions. Military and civilian doctors should also be diligent in their reporting to VAERS of cases of adverse reactions to anthrax vaccine.

Journal ArticleDOI
TL;DR: After a flurry of rulings and counterrulings over whether the vaccine can protect soldiers from inhalation anthrax, a federal court in January lifted a temporary ban on the program, but the debate over the drug’s efficacy is likely to continue as the case moves through the courts.
Abstract: 112 VOLUME 10 | NUMBER 2 | FEBRUARY 2004 NATURE MEDICINE US soldiers are battling with the federal government over the military’s anthrax vaccination scheme. After a flurry of rulings and counterrulings over whether the vaccine can protect soldiers from inhalation anthrax, a federal court in January lifted a temporary ban on the program. But the debate over the drug’s efficacy is likely to continue as the case moves through the courts. The US has vaccinated more than a million soldiers since 1998. Opponents of the program say the vaccine causes both longand shortterm health problems, including pneumonia, joint pain and gastrointestinal disorders. Thousands of adverse event reports have been filed with the US Food and Drug Administration (FDA). However, based on existing evidence, several scientific panels have determined that the vaccine is safe. Those who refuse the shot have been disciplined and, in some cases, court-martialed. No one argues that the vaccine is effective against cutaneous anthrax. A 1962 study—the only placebo-controlled human trial of the anthrax vaccine—followed 1,200 workers in four textile mills. Only 1 of the 26 subsequent cases of anthrax occurred in a fully vaccinated worker, but only 5 of the 26 cases were of inhalation anthrax (Am. J. Public Health 52, 632–645; 1962). Based on those data, a scientific panel in 1973 concluded that inhalation anthrax “occurred too infrequently” to assess the vaccine’s efficacy against it. The panel’s recommendations languished in regulatory limbo, however. They were finally published in 1985, but the FDA never formally adopted or rejected them. In his initial ruling, Judge Emmett Sullivan said the vaccine is an investigational drug being used for an unapproved purpose. He ruled that the US “cannot demand that members of the armed forces also serve as guinea pigs for experimental drugs.” One week later, the FDA published a belated analysis of the 1985 recommendations, disputing the panel’s finding. Analyzing the two exposure routes together, it concluded the vaccine is 92.5% effective against all forms of anthrax. Based on the FDA’s new analysis, the judge lifted the temporary ban. But the new interpretation of the data is a matter of semantics, not science, argues Gene Stollerman, who chaired the 1973 panel. “I will defend our interpretation,” Stollerman says. “Any other interpretation has to do with legal issues.” The existing evidence doesn’t meet the FDA’s usual standards, adds Mark Zaid, the Washington-based lawyer who brought the case against the US Department of Defense (DOD). “When had the FDA ever said to anyone,‘it’s probably effective so we’re going to give you a license’?” Zaid asks. Confident it will prevail, the DOD has ordered a $30 million batch of the vaccine. Laywers for the soldiers, meanwhile, have asked the judge to grant the case class-action status. Tinker Ready, Boston US soldiers refuse to fall in line with anthrax vaccination scheme

Journal ArticleDOI
TL;DR: The histologic and immunofluorescence findings were characteristic of pemphigus vulgaris, and the potential exists for widespread administration of the anthrax vaccine.
Abstract: 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.

Journal Article
TL;DR: This review summarizes the history of anthrax, the need for new vaccines and recent developments in pDNA-based vaccines, leading to the initiation of a human phase I clinical trial in a significantly shorter timeframe than in traditional vaccine development.
Abstract: Over 120 years ago, Pasteur and Greenfield developed an in vitro procedure for producing a live-attenuated Bacillus anthracis bacterial culture capable of protecting livestock from anthrax disease. Since then, anthrax has become one of the best characterized bacterial pathogens with regard to mechanism of toxicity and vaccine development. Most developments have used live-attenuated strains, bacterial supernatants or protein subunit approaches. Recently, novel plasmid DNA (pDNA) approaches to a safe and effective anthrax vaccine have been proposed. This review summarizes the history of anthrax, the need for new vaccines and recent developments in pDNA-based vaccines, leading to the initiation of a human phase I clinical trial in a significantly shorter timeframe than in traditional vaccine development.

Journal ArticleDOI
02 Sep 2004-BMJ
TL;DR: Better vaccines are needed if vaccination is to be made compulsory, according to the World Health Organization (WHO).
Abstract: Better vaccines are needed if vaccination is to be made compulsory T aken at face value the use of vaccines to prevent the effects of serious infections caused by a terrorist attack appears a sensible policy. In 1997 the United States Department of Defense initiated the compulsory anthrax vaccine immunisation programme to immunise 2.4m military personnel.1 In December 2002 a similar programme, also involving civilians, was started against smallpox. In the first five and half months the Department of Defense administered 450 293 doses of smallpox vaccine.2 United States military personnel engaged in military operations in Iraq are immunised against smallpox and anthrax. As in any vaccination campaign, the incidence of the target disease and the characteristics of available vaccines are two key elements in decision making. Naturally occurring anthrax is a rare disease. It occurs mostly in cutaneous form among those exposed to animal products (such as hides) and causes a rare and rapidly fatal—if untreated—respiratory illness (inhalation anthrax). Inhalation anthrax is the most likely form of the disease in the event of a terror attack as the use of anthrax spores for terror or warfare would probably follow dissemination at high concentration by …

Patent
20 Sep 2004
TL;DR: The invention is related to intracellularly induced bacterial DNA promoters and vaccines against Bacillus anthracis as mentioned in this paper, which is a strain of Bacillus Anthracis (Anthracis).
Abstract: The invention is related to intracellularly induced bacterial DNA promoters and vaccines against Bacillus anthracis.

Journal ArticleDOI
TL;DR: Nanoemulsions may serve as useful adjuvants for recombinant anthrax vaccines as an adjuvant for intramuscular (IM) and intranasal (IN) immunization with rPA.
Abstract: Rationale New anthrax vaccines involve immunization with rPA, an immunologic target of antibodies that neutralize anthrax toxin. We have evaluated a non-toxic nanoemulsion as an adjuvant for intramuscular (IM) and intranasal (IN) immunization with rPA. Methods Balb/c mice were immunized with three monthly administrations of 2.5 and 25 ug rPA. The protein was given alone, in a solution of 1% nanoemulsion or with the nanoemulsion and CpG-rich oligonucleotides. Results IM injections of rPA with nanoemulsion resulted in higher titers of anti-PA IgG than IM administration of antigen alone, particularly with low doses of rPA. In contrast, nanoemulsion was absolutely required for the development of immunity after IN administration since anti-PA specific IgA (in bronchial lavage) and IgG (in serum) were observed only in animals receiving in rPA with nanoemulsion, whether or not CpG was present. No animal immunized IM with rPA developed a mucosal antibody response. rPA specific splenocyte activation was demonstrated by proliferative responses in vitro and was accompanied by markedly increased production of INFγ and TNFα, indicating that TH1 responses were induced by the nanoemulsion. Nanoemulsion increased in vitro binding of rPA to dendritic cells but not lymphocytes, suggesting dendritic cells participate in the induction of rPA mucosal immunity after IN immunization. Conclusions Nanoemulsions may serve as useful adjuvants for recombinant anthrax vaccines.

Journal ArticleDOI
23 Oct 2004-BMJ
TL;DR: Editor—Jefferson questions military use of anthrax and smallpox vaccines licensed as safe and effective by the US Food and Drug Administration, which is more extensive and more accurate than cited in the editorial.
Abstract: EDITOR—Jefferson questions military use of anthrax and smallpox vaccines licensed as safe and effective by the US Food and Drug Administration (FDA).1 The Department of Defense is concerned about the safety of US service members, so we vaccinate them to keep them healthy. Vaccination provides the only round the clock protection against the malicious use of microbes as weapons. Our vaccination programmes are based …

Journal ArticleDOI
TL;DR: The data obtained in this preliminary study indicated that extractable cell-wall antigens obtained from the vegetative form of B. anthracis may be used for skin tests and in-vitro testing of specific humoral and cell-mediated anthrax immunity.

Journal ArticleDOI
06 May 2004-Nature
TL;DR: A US government programme to bolster public defences against bioterrorism will soon give out its first grants — despite complaints from the biotechnology industry that the programme is not working as intended.

Journal ArticleDOI
TL;DR: Treatment with zinc gluconate at a dose level of 60 mg zinc per day for a few months subsequently led to the complete reversal of hair loss in this case.
Abstract: A USA Air Force Master Sergeant suffered severe hair loss from the scalp and face a few weeks after receipt of his fifth dose of anthrax vaccine. He also suffered from a reduction in his eyesight, insomnia, headaches, involuntary twitches of the right arm muscle, and memory loss. In addition, he felt chronically tired, had hot and cold flashes on his head, and cold flashes on the back of his neck. My investigation of this case revealed that hair loss and serious systemic illness have also been reported by some other individuals who received anthrax vaccine and other vaccines. Differential diagnosis was used to evaluate the medical evidence in this case to identify the causes of illness and hair loss. Treatment with zinc gluconate at a dose level of 60 mg zinc per day for a few months subsequently led to the complete reversal of hair loss in this case. It is plausible that vaccines induced a stage of zinc deficiency by activating the immune system and increased the utilization of zinc. Zinc is an essential element required for hair metabolism and the activation of the immune system. © Copyright 2004, Pearblossom Private School, Inc.–Publishing Division. All rights reserved.

Journal Article
TL;DR: The lifecycle and biology of this micro-organism is reviewed, and the range of illness caused by B. anthracis from the molecular level to the clinical symptoms is discussed.
Abstract: Anthrax caused by Bacillus anthracis in humans is rare. Two recent outbreaks that were intentionally caused occurred among postal employees, politicians, and journalists in the United States. This has caused tremendous fear, and our experience with these "anthrax incidents" has changed our views on the natural history of this disease in people. In this paper, we review the lifecycle and biology of this micro-organism. Anthrax that occurs from a weaponized form of this micro-organism has a specific clinical presentation that requires a suspicion of anthrax exposure to be diagnosed. New methods of testing for anthrax have been developed and may simplify diagnosis in the future. The range of illness caused by B. anthracis from the molecular level to the clinical symptoms is discussed. We also review the diagnostic criteria and differential diagnosis as well as treatment of this condition.

Journal Article
TL;DR: The antibody-mediated enhancement of the anthrax lethal action is a convincing argument for further development of a new-generation anthrax vaccine and definition of the linear antigen determinants for neutralizing antibodies in the protective antigens is an important step in the development of the next-generation vaccine.
Abstract: Anthrax belongs to highly dangerous infections of man and animals. No effective treatment methods for pulmonary types of the disease have been yet developed. The existing anthrax vaccines were designed decades ago and need improvement to fit the large-scale vaccination of population. At the same time, the immunological properties of the anthrax vaccine main component, i.e. of the protective agent, have been poorly studied. We obtained, within the present case study, a panel of mouse monoclonal antibodies to the protective agent and investigated the properties of the highest-affine panel representatives. An unusual phenomenon was detected, which is related with enhancement of the anthrax toxin action on the mouse macrophage-like cell-line in presence of the 1F2 monoclonal antibody. The remaining analyzed antibodies, i.e. 6G8 and 6G7, were found to neutralize effectively the toxin action. The enhancing and neutralizing antibodies were proven to be specific to different domains of the protective antigen and to recognize epitopes in its composition. The antibody-mediated enhancement of the anthrax lethal action is a convincing argument for further development of a new-generation anthrax vaccine. Definition of the linear antigen determinants for neutralizing antibodies in the protective antigens is an important step in the development of the next-generation anthrax vaccine.

Journal Article
TL;DR: The gene encoding anthrax lehtal factor (LF) was cloned into a secretory expression plasmid and then expressed in periplasmic space of E. coli, and sequencing assay showed that the N-terminal amino acid sequence of rLF was identical to the N -terminal sequence of natural LF.
Abstract: The gene encoding anthrax lehtal factor (LF) was cloned into a secretory expression plasmid and then expressed in periplasmic space of E. coli. The recombinant LF (rLF) expressed was about 4% of the total proteins in E. coli. About 3 mg electrophoresis purity rLF could be obtained after the purification of 1 liter culure using ion exchange chromatography and gel filtration. The result of sequencing assay showed that the N-terminal amino acid sequence of rLF was identical to the N-terminal sequence of natural LF. In vitro toxicity analysis also shows that rLF has an excellent biological activity. The successful expression of rLF has placed a solid foundation for the research on toxicity mechanism of LF, developing new anthrax vaccines, and screening for inhibitors against anthrax toxin.