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Showing papers on "Anthrax vaccines published in 2011"


Journal ArticleDOI
TL;DR: Although anthrax is acknowledged as a toxinogenic disease, additional factors, other than the bacterial toxin, may be involved in the virulence of B. anthracis and may be needed for the long‐lasting protection conferred by PA immunization.
Abstract: The lethal anthrax disease is caused by spores of the gram-positive Bacillus anthracis, a member of the cereus group of bacilli. Although the disease is very rare in the Western world, development of anthrax countermeasures gains increasing attention due to the potential use of B. anthracis spores as a bio-terror weapon. Protective antigen (PA), the non-toxic subunit of the bacterial secreted exotoxin, fulfills the role of recognizing a specific receptor and mediating the entry of the toxin into the host target cells. PA elicits a protective immune response and represents the basis for all current anthrax vaccines. Anti-PA neutralizing antibodies are useful correlates for protection and for vaccine efficacy evaluation. Post exposure anti-toxemic and anti-bacteremic prophylactic treatment of anthrax requires prolonged antibiotic administration. Shorter efficient postexposure treatments may require active or passive immunization, in addition to antibiotics. Although anthrax is acknowledged as a toxinogenic disease, additional factors, other than the bacterial toxin, may be involved in the virulence of B. anthracis and may be needed for the long-lasting protection conferred by PA immunization. The search for such novel factors is the focus of several high throughput genomic and proteomic studies that are already leading to identification of novel targets for therapeutics, for vaccine candidates, as well as biomarkers for detection and diagnosis.

78 citations


Journal ArticleDOI
TL;DR: The incidence of the disease has decreased in developed countries as a result of vaccination and improved industrial hygiene, and administration of anti-protective antigen (PA) antibody in combination with ciprofloxacin produced 90%-100% survival.
Abstract: Anthrax is a zoonotic disease caused by Bacillus anthracis. It is potentially fatal and highly contagious disease. Herbivores are the natural host. Human acquire the disease incidentally by contact with infected animal or animal products. In the 18th century an epidemic destroyed approximately half of the sheep in Europe. In 1900 human inhalational anthrax occured sporadically in the United States. In 1979 an outbreak of human anthrax occured in Sverdlovsk of Soviet Union. Anthrax continued to represent a world wide presence. The incidence of the disease has decreased in developed countries as a result of vaccination and improved industrial hygiene. Human anthrax clinically presents in three forms, i.e. cutaneous, gastrointestinal and inhalational. About 95% of human anthrax is cutaneous and 5% is inhalational. Gastrointestinal anthrax is very rare (less than 1%). Inhalational form is used as a biological warefare agent. Penicillin, ciprofloxacin (and other quinolones), doxicyclin, ampicillin, imipenem, clindamycin, clarithromycin, vancomycin, chloramphenicol, rifampicin are effective antimicrobials. Antimicrobial therapy for 60 days is recommended. Human anthrax vaccine is available. Administration of anti-protective antigen (PA) antibody in combination with ciprofloxacin produced 90%-100% survival. The combination of CPG-adjuvanted anthrax vaccine adsorbed (AVA) plus dalbavancin significantly improved survival.

56 citations


Journal ArticleDOI
TL;DR: Genetic associations between the immunoglobulin G antibody to protective antigen (AbPA) response to Anthrax Vaccine Adsorbed (AVA) in humans, and polymorphisms at HLA class I and class II loci are searched for.
Abstract: Host genetic variation, particularly within the human leukocyte antigen (HLA) loci, reportedly mediates heterogeneity in immune response to certain vaccines; however, no large study of genetic determinants of anthrax vaccine response has been described. We searched for associations between the immunoglobulin G antibody to protective antigen (AbPA) response to Anthrax Vaccine Adsorbed (AVA) in humans, and polymorphisms at HLA class I (HLA-A, -B, and -C) and class II (HLA–DRB1, –DQA1, –DQB1, –DPB1) loci. The study included 794 European-Americans and 200 African-Americans participating in a 43-month, double-blind and placebo-controlled clinical trial of AVA (clinicaltrials.gov identifier NCT00119067). Among European-Americans, genes from tightly linked HLA–DRB1, –DQA1, –DQB1 haplotypes displayed significant overall associations with longitudinal variation in AbPA levels at 4, 8, 26 and 30 weeks from baseline in response to vaccination with three or four doses of AVA (global P=6.53 × 10−4). In particular, carriage of the DRB1–DQA1–DQB1 haplotypes *1501–*0102–*0602 (P=1.17 × 10−5), *0101–*0101–*0501 (P=0.009) and *0102–*0101–*0501 (P=0.006) was associated with significantly lower AbPA levels. In carriers of two copies of these haplotypes, lower AbPA levels persisted following subsequent vaccinations. No significant associations were observed amongst African-Americans or for any HLA class I allele/haplotype. Further studies will be required to replicate these findings and to explore the role of host genetic variation outside of the HLA region.

35 citations


Journal ArticleDOI
29 Jan 2011-Vaccine
TL;DR: Three nonproprietary liposome formulations containing monophosphoryl lipid A each induced 3-fold to 5-fold increased titers of binding and neutralizing antibodies to anthrax protective antigen compared to aluminum hydroxide-adsorbed antigen in monkeys.

35 citations


Journal ArticleDOI
TL;DR: A comprehensive review of current research in drug discovery is presented in this article, including efforts to improve the purity and stability of vaccines, design inhibitors targeting the anthrax toxins, and identify inhibitors of novel enzyme targets.
Abstract: Bacillus anthracis, the causative agent responsible for anthrax infections, poses a significant biodefense threat. There is a high mortality rate associated with untreated anthrax infections; specifically, inhalation anthrax is a particularly virulent form of infection with mortality rates close to 100%, even with aggressive treatment. Currently, a vaccine is not available to the general public and few antibiotics have been approved by the FDA for the treatment of inhalation anthrax. With the threat of natural or engineered bacterial resistance to antibiotics and the limited population for whom the current drugs are approved, there is a clear need for more effective treatments against this deadly infection. A comprehensive review of current research in drug discovery is presented in this article, including efforts to improve the purity and stability of vaccines, design inhibitors targeting the anthrax toxins, and identify inhibitors of novel enzyme targets. High resolution structural information for the anthrax toxins and several essential metabolic enzymes has played a significant role in aiding the structure-based design of potent and selective antibiotics.

34 citations


Journal ArticleDOI
TL;DR: It is demonstrated that antibiotic treatment can prevent the development of fatal disease in respiratory-anthrax-infected animals and can cure animals after disease establishment.
Abstract: Respiratory anthrax, in the absence of early antibiotic treatment, is a fatal disease. This study aimed to test the efficiency of antibiotic therapy in curing infected animals and those sick with anthrax. Postexposure prophylaxis (24 h postinfection [p.i.]) of guinea pigs infected intranasally with Bacillus anthracis Vollum spores with doxycycline, ofloxacin, imipenem, and gentamicin conferred protection. However, upon termination of treatment, the animals died from respiratory anthrax. Combined treatment with antibiotics and active vaccination with a protective antigen-based vaccine leads to full protection even after cessation of treatment. Delaying the initiation of antibiotic administration to over 24 h p.i. resulted in treatment of animals with anthrax exhibiting various degrees of bacteremia and toxemia. Treatment with doxycycline or ciprofloxacin cured sick guinea pigs and rabbits exhibiting bacteremia levels up to 10(5) CFU/ml. Addition of anti-protective antigen (PA) antibodies augmented the efficiency of protection, allowing the cure of guinea pigs and rabbits with 10- to 20-fold-higher bacteremia levels, up to 7 × 10(5) CFU/ml and 2 × 10(6) CFU/ml, respectively. Treatment with ciprofloxacin and a monoclonal anti-PA antibody rescued rabbits with bacteremia levels up to 4 × 10(6) CFU/ml. During antibiotic administration, all surviving animals developed a protective immune response against development of a fatal disease and subcutaneous challenge with Vollum spores. In conclusion, these results demonstrate that antibiotic treatment can prevent the development of fatal disease in respiratory-anthrax-infected animals and can cure animals after disease establishment. A therapeutic time window of 40 h to 48 h from infection to initiation of efficient antibiotic-mediated cure was observed.

31 citations


Journal ArticleDOI
TL;DR: The ability of human LF-specific antibodies to neutralize toxin activity supports the possible inclusion of LF in future anthrax vaccines, suggesting the possibility that they may contribute to protection.
Abstract: Bacillus anthracis, the causative agent of anthrax, produces a tripartite toxin composed of two enzymatically active subunits, lethal factor (LF) and edema factor (EF), which, when associated with a cell-binding component, protective antigen (PA), form lethal toxin and edema toxin, respectively. In this preliminary study, we characterized the toxin-specific antibody responses observed in 17 individuals infected with cutaneous anthrax. The majority of the toxin-specific antibody responses observed following infection were directed against LF, with immunoglobulin G (IgG) detected as early as 4 days after the onset of symptoms in contrast to the later and lower EF- and PA-specific IgG responses. Unlike the case with infection, the predominant toxin-specific antibody response of those immunized with the US anthrax vaccine absorbed and UK anthrax vaccine precipitated licensed anthrax vaccines was directed against PA. We observed that the LF-specific human antibodies were, like anti-PA antibodies, able to neutralize toxin activity, suggesting the possibility that they may contribute to protection. We conclude that an antibody response to LF might be a more sensitive diagnostic marker of anthrax than to PA. The ability of human LF-specific antibodies to neutralize toxin activity supports the possible inclusion of LF in future anthrax vaccines.

30 citations


Journal ArticleDOI
09 May 2011-Vaccine
TL;DR: Improved understanding of the fine specificities of humoral immune responses that provide optimum neutralization capacity may enhance the efficacy of future passive immune globulin preparations to treat and prevent inhalation anthrax morbidity and mortality.

25 citations


Journal ArticleDOI
TL;DR: Characterization of a bispecific monoclonal antibody, H10, which showed high affinity interaction with both edema factor and lethal factor of B. anthracis and gave 100% protection to mice from in vivo challenge with lethal toxin and edema toxin is reported.

23 citations


Journal ArticleDOI
TL;DR: The studies show the applicability of the human mouse heteromyeloma cell line CB-F7 line to create fully human monoclonal antibodies for vaccination and suggest the binding of the monOClonal antibody to the peptide regions 121-150 or 451-470 of LF.

16 citations


Journal ArticleDOI
TL;DR: The results showed that the combination of CIA05 and alum significantly increased both serum anti-PA IgG antibody and toxin-neutralizing antibody titers, and the adjuvant effects were greater when lower antigen doses were used for immunization.

Journal ArticleDOI
TL;DR: A toxin neutralization assay (TNA) can detect a decrease in the immunogenicity of anthrax vaccines as a consequence of brief exposure to elevated temperature, which may help in adopting Immunogenicity as a replacement of the current potency test.
Abstract: We report that a toxin neutralization assay (TNA) can detect a decrease in the immunogenicity of anthrax vaccines as a consequence of brief exposure to elevated temperature. This attribute of TNA may help in adopting immunogenicity as a replacement of the current potency test, which involves protection from lethal challenge.

Journal ArticleDOI
TL;DR: Results open the possibility that an immunogenicity test in which TNA is used to quantify the anti-PA antibody responses can be used to measure vaccine potency of anthrax vaccines at the end of the manufacturing process and periodically after the finished product has been placed in storage, instead of an active protection test that requires lethal challenge.

Journal ArticleDOI
TL;DR: The recent progress in the direction of anthrax prophylaxis has been evaluated and DNA vaccination resulted in varying degree of protection and seems a promising approach.
Abstract: Bacillus anthracis is the etiological agent of anthrax. Although anthrax is primarily an epizootic disease; humans are at risk for contracting anthrax. The potential use of B. anthracis spores as biowarfare agent has led to immense attention. Prolonged vaccination schedule of current anthrax vaccine and variable protection conferred; often leading to failure of therapy. This highlights the need for alternative anthrax countermeasures. A number of approaches are being investigated to substitute or supplement the existing anthrax vaccines. These relied on expression of Protective antigen (PA), the key protective immunogen; in bacterial or plant systems; or utilization of attenuated strains of B. anthracis for immunization. Few studies have established potential of domain IV of PA for immunization. Other targets including the spore, capsule, S-layer and anthrax toxin components have been investigated for imparting protective immunity. It has been shown that co-immunization of PA with domain I of lethal factor that binds PA resulted in higher antibody responses. Of the epitope based vaccines, the loop neutralizing determinant, in particular; elicited robust neutralizing antibody response and conferred 97% protection upon challenge. DNA vaccination resulted in varying degree of protection and seems a promising approach. Additionally, the applicability of monoclonal and therapeutic antibodies in the treatment of anthrax has also been demonstrated. The recent progress in the direction of anthrax prophylaxis has been evaluated in this review.

Journal ArticleDOI
02 Sep 2011-Science
TL;DR: In the wake of the fall 2001 anthrax letter attacks, protecting against future bioterrorism attacks became a top priority for the U.S. government, resulting in the creation of Project BioShield, which still has no doses of a next-generation anthrax vaccine, nor any vaccines or drugs to defend against Ebola or plague.
Abstract: Biodefense: 10 Years AfterIn the wake of the fall 2001 anthrax letter attacks, protecting against future bioterrorism attacks became a top priority for the U.S. government, resulting in the creation of Project BioShield. This effort was intended to make available effective vaccines and treatments against agents like anthrax, botulinum toxin, Ebola, and plague. Yet to this day, the Strategic National Stockpile—a repository of medicines for use in a public health emergency—has no doses of a next-generation anthrax vaccine, nor any vaccines or drugs to defend against Ebola or plague. No major pharmaceutical companies have supplied Project BioShield, and the small biotech companies involved often have had difficulty with large-scale manufacturing and regulatory issues. Congress has also transferred $1.4 billion of BioShield money—more than 25%—to other projects.

Journal ArticleDOI
09 Aug 2011-Toxins
TL;DR: This report investigates the process by which a human monoclonal antibody specific for the amino-terminal domain of PA neutralizes lethal toxin in an in vitro assay of cytotoxicity, and finds that it neutralizes LT by blocking the requisite cleavage of the amino -terminal 20 kD portion of the molecule (PA20) from the remainder of the PA monomer.
Abstract: The primary immunogenic component of the currently approved anthrax vaccine is the protective antigen (PA) unit of the binary toxin system. PA-specific antibodies neutralize anthrax toxins and protect against infection. Recent research has determined that in humans, only antibodies specific for particular determinants are capable of effecting toxin neutralization, and that the neutralizing epitopes recognized by these antibodies are distributed throughout the PA monomer. The mechanisms by which the majority of these epitopes effect neutralization remain unknown. In this report we investigate the process by which a human monoclonal antibody specific for the amino-terminal domain of PA neutralizes lethal toxin in an in vitro assay of cytotoxicity, and find that it neutralizes LT by blocking the requisite cleavage of the amino-terminal 20 kD portion of the molecule (PA20) from the remainder of the PA monomer. We also demonstrate that the epitope recognized by this human monoclonal does not encompass the 166RKKR169 furin recognition sequence in domain 1 of PA.

Journal ArticleDOI
TL;DR: These are the observations of a physician who has evolved from an emergency medicine ( response-based) posture to one of protecting the health of the community through smart policy and preventive services.
Abstract: To the Editor With the 10-year anniversary of the multiwave, multisite, lethal anthrax attacks, it makes sense to reflect on the lessons that have been learned from this experience and assess current priorities on biodefense preparedness and community resilience. What follows are the observations of a physician who has evolved from an emergency medicine (response-based) posture to one of protecting the health of the community through smart policy and preventive services.

Journal ArticleDOI
TL;DR: This antibiotic marker-free strain and the correlative experiment method may have potential applications for the generation of a live attenuated anthrax vaccine.
Abstract: Extracellular antigen 1 (EA1), a major component of the Bacillus anthracis surface layer (S-layer), was used as a fusion partner for the expression of heterologous antigen. A recombinant B. anthracis strain was constructed by integrating a translational fusion harboring the DNA fragments encoding the cell wall–targeting domain of the S-layer protein EA1 and the 20-kDa N-terminal fragment of anthrax protective antigen (PA20) into the chromosome. A thermosensitive plasmid expressing Cre recombinase was introduced at a permissive temperature to remove the antibiotic marker. Cre recombinase action at the loxP sites excised the spectinomycin resistance cassette. The final derivative strains were analyzed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis, Western blot analysis, and immunofluorescence analysis. PA20 was successfully expressed on the S-layer of the recombinant antibiotic marker-free strain. Guinea pigs were immunized with the attenuated recombinant B. anthracis strain, and the bacilli elicited a humoral response to PA20. This antibiotic marker-free strain and the correlative experiment method may have potential applications for the generation of a live attenuated anthrax vaccine.

Journal ArticleDOI
TL;DR: In the months leading up to the 10th anniversary of the September 11 terrorist attacks and subsequent anthrax attacks, I was asked by various colleagues to address anthrax in my editorial, but deferred for several reasons.
Abstract: In the months leading up to the 10th anniversary of the September 11 terrorist attacks and subsequent anthrax attacks, I was asked by various colleagues to address anthrax in my editorial. I deferred for several reasons. First, the journal was in receipt of a commentary on the work of the Bipartisan WMD (weapons of mass destruction) Terrorism Research Center by former Senators Bob Graham and Jim Talent, who are leading that endeavor.1 Having served as an advisor to the center on their “report card” project, I believed the commentary would be a more appropriate vehicle for highlighting the important work that is being done—and not being done—on anthrax and other potentially serious infectious diseases since the events of September 11, 2001. Second, Dr Tom Zink addressed several important issues concerning anthrax that the editors believed would not be articulated well in an editorial.2 Finally, although the letter(s) that initiated the anthrax attack in 2001 may have been postmarked in September of that year, to those of us who dealt directly with the medical and public health consequences of that event, the true 10th anniversary is not September 11 but October 4, 2001. That was the day of the press conference at JFK Medical Center in Atlantis, Florida, announcing what would prove to be the first diagnosed case of anthrax resulting from the “Amerithrax” attack.3

Journal ArticleDOI
TL;DR: In additional immunogenicity experiments neither the magnitude of the response to a single dose of vaccine, nor the estimation of the dose necessary to induce a measurable response were able to consistently detect brief exposure of vaccines to potentially damaging temperatures.

Journal ArticleDOI
04 Nov 2011-Science
TL;DR: Last week, the full National Biodefense Science Board voted 12–1 in favor of a trial assuming its ethics are approved by a review board, saying that it was too uneasy to risk a mass science experiment on thousands of children after a bioterror strike.
Abstract: Should children be enrolled in a clinical trial of the anthrax vaccine, which is almost certain not to help them and may harm them? Or should the U.S. government gamble and wait for a possible attack before exposing children to the vaccine for the very first time? Last week, the full National Biodefense Science Board voted 12–1 in favor of a trial assuming its ethics are approved by a review board, saying that it was too uneasy to risk a mass science experiment on thousands of children after a bioterror strike, even if some consider that possibility remote.

Journal ArticleDOI
TL;DR: The aim of this study was to investigate the role of quorum sensing in Bacillus anthracis growth and toxin production and to establish an experimental procedure to measure the response of the immune system to Bacillus Anthracis toxins.
Abstract: Aim: The aim of this study was to investigate the role of quorum sensing in Bacillus anthracis growth and toxin production. Methods and Results: A microwell plate culture method was developed to simulate the normal UK-licensed anthrax vaccine production run. Once established, sterile supernatant additions from a previous B. anthracis culture were made, and reductions in lag phase and early stimulation of the anthrax toxin component protective antigen (PA) were monitored using ELISA. The addition of the quorum-sensing inhibitor, fur-1, prolonged the lag phase and impeded PA production. Spin filters of various sizes were used to identify the molecular weight fraction of the sterile supernatant responsible for the autoinducer effect. A weight fraction between 5 and 10 kDa was responsible for the autoinducer effect; however, further identification using mass spectroscopy proved inconclusive. Conclusions: Quorum sensing mediated by the autoinducer two molecule plays a significant role in both B. anthracis growth and toxin production. Significance and Impact of the study: While genomic analysis has eluded to the importance of LuxS and quorum sensing in anthrax, this is the first analysis using a production strain of B. anthracis and a quorum-sensing inhibitor to monitor the effect on growth and toxin production. This gives insights into anthrax pathogenicity and vaccine manufacture.

Reference EntryDOI
16 May 2011
TL;DR: Charles Chamberland was an associate of Louis Pasteur whose technical skills and inventive mind added significantly to the experimental investigations of chicken cholera, anthrax, swine erysipelas and rabies and the development of vaccines produced by the Pasteur Institute.
Abstract: Charles Chamberland was an associate of Louis Pasteur whose technical skills and inventive mind added significantly to the experimental investigations of chicken cholera, anthrax, swine erysipelas and rabies and the development of vaccines produced by the Pasteur Institute. Trained in physics and mathematics rather than biology or medicine, he is credited with the invention of the first laboratory autoclave and the Chamberland–Pasteur porcelain filter. His laboratory of applied microbiology within the Pasteur Institute had the major responsibility for producing commercial anthrax vaccines and advising satellite Pasteur institutes. Keywords: Charles Chamberland; Louis Pasteur; Pasteur Institute; anthrax vaccine; commercial vaccines; autoclave; Chamberland–Pasteur filter

Patent
08 Nov 2011
TL;DR: In this paper, the same day identification of anthrax edema factor was proposed, which can reduce diagnosis time to as little as four hours and significantly increase the odds of delivering proper treatment and patient recovery.
Abstract: One major problem in diagnosis methods presently available for anthrax is that these methods require several days to produce a result, are rendered unusable after antibiotic use, or are not quantifiable. The only existing treatment for anthrax requires administration soon after infection at a time when patients are exhibiting only mild flu-like symptoms. Thus, by the time a diagnosis is made a patient may be days beyond the time when treatment would be effective. The present invention reduces diagnosis time to as little as four hours providing same day identification of anthrax radically increasing the odds of delivering proper treatment and patient recovery. The rapid identification of anthrax edema factor activity exhibited by the invention is also amenable to in vivo screening protocols for the discovery and development of anthrax vaccines, anti-toxins and edema factor inhibitors. The invention isolates and concentrates edema factor and edema toxin from nearly any sample. By capitalizing on the adenylate cyclase activity of edema factor the invention amplifies output signals producing reliable detection of low concentrations of edema factor previously unachievable. The invention involves novel purification and detection techniques and substrates for rapid, reproducible, and quantitative measurements of anthrax edema factor, and other adenylate cyclases in biological samples.

Journal ArticleDOI
TL;DR: An asporogenic recombinant strain Bacillus anthracis 55ΔTPA-1(Spo−) producing anthrax protective antigen (PA) was obtained and preserves asporogenicity and ability to replicate the hybrid plasmid after in vitro passages.
Abstract: An asporogenic recombinant strain Bacillus anthracis 55ΔTPA-1(Spo−) producing anthrax protective antigen (PA) was obtained. The strain contains structural gene pag as a part of a hybrid replicon pUB110PA-1 and lacks determinants encoding the synthesis of main factors of anthrax pathogenicity. The level of PA production by asporogenic genetically engineered strain is approximately 80 μg/ml that is 4–5 times more than the values determined for vaccine strains B. anthracis STI-1 and B. anthracis 55. The strain preserves asporogenicity and ability to replicate the hybrid plasmid after in vitro passages. Biologically active PA was isolated from the constructed strain B. anthracis 55ΔTPA-1(Spo−). Double immunization of rabbits with 50 μg of the purified recombinant product provides their 100% protection from infection with 50 LD50 of a highly virulent anthrax strain.

Journal ArticleDOI
TL;DR: KNIH is planning to receive a conditional licensure from Korea Food and Drug Administration and to start stockpiling of this vaccine for emergency use, a second generation vaccine of which major component is a purified recombinant PA.
Abstract: Anthrax has been considered one of most likely bio-warfare weapons. It’s potential use as an agent of bio-terrorism was highlighted in 2001 by a series of postal mailing attacks in United States. Anthrax is a highly lethal infectious disease caused by the spore-forming bacterium Bacillus anthracis. After entering the host, anthrax spores germinate inside macrophages, which transport the bacteria to regional lymph nodes. Released bacilli then multiply extracellularly, secrete high levels of exotoxins, and spread systemically in the bloodstream. The exotoxin is composed of three distinct proteins, protective antigen (PA), edema factor (EF), and lethal factor (LF), which are secreted separately as nontoxic monomers. The binding of LF or EF to PA results in formation of active lethal toxin or edema toxin, respectively, which causes massive edema and organ failure. Among these toxin proteins, because PA can elicit a protective immune response against both anthrax toxins, it is the target antigen of existing anthrax vaccines. Current human anthrax vaccines available in the US and Europe consist of alum-precipitated supernatant material from cultures of a toxigenic, nonencapsulated strain of B. anthracis. The major component of human anthrax vaccine that confers protection is PA. A second generation human vaccine using the recombinant PA is being developed. In 2002, Korea National Institute of Health (KNIH) started to develop human anthrax vaccine for national stockpiling against an emergency situation, The developing vaccine is a second generation vaccine of which major component is a purified recombinant PA. For a mass production of the PA from B. anthracis, KNIH established an expression system with Bacillus brevis - pNU212 and developed functional assays and animal models for vaccine efficacy tests. With the cooperation of a private sector, Green Cross Co., the development of manufacturing process, preclinical and clinical trial phase I studies were completed. In 2011, clinical trial phase II study will be started in Seoul National Hospital, Seoul Korea. After clinical studies, KNIH is planning to receive a conditional licensure from Korea Food and Drug Administration and to start stockpiling of this vaccine for emergency use.

01 Jan 2011
TL;DR: A recombinant B. anthracis strain was constructed by integrating a translational fusion harboring the DNA fragments encoding the cell wall-targeting domain of the S-layer protein EA1 and the 20-kDa N-ter-minal fragment of anthrax protective antigen (PA20) into the chromosome.
Abstract: Extracellular antigen 1 (EA1), a major com- ponent of the Bacillus anthracis surface layer (S-layer), was used as a fusion partner for the expression of heter- ologous antigen. A recombinant B. anthracis strain was constructed by integrating a translational fusion harboring the DNA fragments encoding the cell wall-targeting domain of the S-layer protein EA1 and the 20-kDa N-ter- minal fragment of anthrax protective antigen (PA20) into the chromosome. A thermosensitive plasmid expressing Cre recombinase was introduced at a permissive tempera- ture to remove the antibiotic marker. Cre recombinase action at the loxP sites excised the spectinomycin resis- tance cassette. The final derivative strains were analyzed by sodium dodecyl sulfate-polyacrylamide gel electro- phoresis, Western blot analysis, and immunofluorescence analysis. PA20 was successfully expressed on the S-layer of the recombinant antibiotic marker-free strain. Guinea pigs were immunized with the attenuated recombinant B. anthracis strain, and the bacilli elicited a humoral response to PA20. This antibiotic marker-free strain and the correlative experiment method may have potential applications for the generation of a live attenuated anthrax vaccine.