Anthrax vaccines: past, present and future.
TL;DR: Most livestock vaccines in use throughout the world today for immunization against anthrax are derivatives of the live spore vaccine formulated by Sterne in 1937 and still use descendants of his strain 34F2, and room for development of a successor is discussed.
About: This article is published in Vaccine.The article was published on 1991-08-01. It has received 334 citations till now. The article focuses on the topics: Anthrax vaccines & Anthrax Vaccine Adsorbed.
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TL;DR: A consensus-based recommendation for measures to be taken by medical and public health professionals following the use of anthrax as a biological weapon against a civilian population was developed by a working group of 21 representatives from staff of major academic medical centers and research as mentioned in this paper.
Abstract: Objective To develop consensus-based recommendations for measures to be taken by medical and public health professionals following the use of anthrax as a biological weapon against a civilian population. Participants The working group included 21 representatives from staff of major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. Evidence MEDLINE databases were searched from January 1966 to April 1998, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of references identified by this search led to identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. Consensus Process The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. Members of the working group provided formal written comments which were incorporated into the second draft of the statement. The working group reviewed the second draft on June 12, 1998. No significant disagreements existed and comments were incorporated into a third draft. The fourth and final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. Conclusions Specific consensus recommendations are made regarding the diagnosis of anthrax, indications for vaccination, therapy for those exposed, postexposure prophylaxis, decontamination of the environment, and additional research needs.
835 citations
TL;DR: Serial passage experiments show that within-host competition generally drives an increase in a parasite's virulence in a new host, whereas the parasite becomes avirulent to its former host, indicating a trade-off between parasite fitnesses on different hosts.
Abstract: Serial passage experiments are a form of experimental evolution that is frequently used in applied sciences; for example, in vaccine development. During these experiments, molecular and phenotypic evolution can be monitored in real time, providing insights into the causes and consequences of parasite evolution. Within-host competition generally drives an increase in a parasite's virulence in a new host, whereas the parasite becomes avirulent to its former host, indicating a trade-off between parasite fitnesses on different hosts. Understanding why parasite virulence seldom escalates similarly in natural populations could help us to manage virulence and deal with emerging diseases.
520 citations
TL;DR: This group of organisms represents microbes of high economic, medical and biodefense importance and contains the highest number of closely related fully sequenced genomes, giving the unique opportunity for thorough comparative genomic analyses.
Abstract: Members of the Bacillus cereus group of organisms include Bacillus cereus, Bacillus anthracis and Bacillus thuringiensis. Collectively, these organisms represent microbes of high economic, medical and biodefense importance. Given this significance, this group contains the highest number of closely related fully sequenced genomes, giving the unique opportunity for thorough comparative genomic analyses. Much of the disease and host specificity of members of this group can be attributed to their plasmids, which vary in size and number. Chromosomes exhibit a high level of synteny and protein similarity, with limited differences in gene content, questioning the speciation of the group members. Genomic data have spurred functional studies that combined microarrays and proteomics. Recent advances are reviewed in this article and highlight the advantages of genomic approaches to the study of this important group of bacteria.
487 citations
Cites background from "Anthrax vaccines: past, present and..."
...It is avirulent but maintains anthrax toxin production and is the derivative of most livestock vaccines in use throughout the world [44]....
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TL;DR: The use of Bacillus subtilis to express antigens that can be administered either intranasally or sublingually is providing new insights in the area of mucosal vaccines, and advances will help to accelerate the development and testing of new mucosalvaccines against many human and animal diseases.
Abstract: Most pathogens enter the body through mucosal surfaces. Mucosal immunization, a non-invasive needle-free route, often stimulates a mucosal immune response that is both effective against mucosal and systemic pathogens. The development of mucosally administered heat-stable vaccines with long shelf life would therefore significantly enhance immunization programs in developing countries by avoiding the need for a cold chain or systemic injections. Currently, recombinant vaccine carriers are being used for antigen delivery. Engineering Bacillus subtilis for use as a non-invasive and heat stable antigen delivery system has proven successful. Bacterial spores protected by multiple layers of protein are known to be robust and resistant to desiccation. Stable constructs have been created by integration into the bacterial chromosome of immunogens. The spore coat has been used as a vehicle for heterologous antigen presentation and protective immunization. Sublingual (SL) and intranasal (IN) routes have recently received attention as delivery routes for therapeutic drugs and vaccines and recent attempts by several investigators, including our group, to develop vaccines that can be delivered intranasally and sublingually have met with a lot of success.
As discussed in this Review, the use of Bacillus subtilis to express antigens that can be administered either intranasally or sublingually is providing new insights in the area of mucosal vaccines. In our work, we evaluated the efficacy of SL and IN immunizations with B. subtilis engineered to express tetanus toxin fragment C (TTFC) in mice and piglets. These bacteria engineered to express heterologous antigen either on the spore surface or within the vegetative cell have been used for oral, IN and SL delivery of antigens. A Bacillus subtilis spore coat protein, CotC was used as a fusion partner to express the tetanus fragment C. B. subtilis spores known to be highly stable and safe are also easy to purify making this spore-based display system a potentially powerful approach for surface expression of antigens. These advances will help to accelerate the development and testing of new mucosal vaccines against many human and animal diseases.
345 citations
TL;DR: The purification and the characterization of an immunodominant protein of the spore surface was described and this collagen‐like surface protein was named BclA (for Bacillus c ollagen‐ l ike protein of anthracis).
Abstract: Bacillus anthracis, the aetiological agent of anthrax, is a Gram-positive spore-forming bacterium. The exosporium is the outermost integument surrounding the mature spore. Here, we describe the purification and the characterization of an immunodominant protein of the spore surface. This protein was abundant, glycosylated and part of the exosporium. The amino-terminal sequence was determined and the corresponding gene was identified. It encodes a protein of 382 amino acid residues, the central part of which contains a region of GXX motifs presenting similarity to mammalian collagen proteins. Thus, this collagen-like surface protein was named BclA (for Bacillus collagen-like protein of anthracis). BclA was absent from vegetative cells; it was detected only in spores and sporulating cells. A potential promoter, dependent on the sigma factor sigma(K), which is required for a variety of events late in sporulation, was found upstream from the bclA gene. A bclA deletion mutant was constructed and analysed. Electron microscopy studies showed that BclA is a structural component of the filaments covering the outer layer of the exosporium.
334 citations
Cites background from "Anthrax vaccines: past, present and..."
...It is used widely and efficiently as a live veterinary vaccine against anthrax (Turnbull, 1991; Mock and Fouet, 2001)....
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...For human use, cell-free vaccines, consisting of protective antigen (PA) the common cell-binding toxin component, have been developed (Turnbull, 1991)....
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References
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TL;DR: It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1] produced by Bacillus anthracis in an inactive form and nearly equals that of the most active known cyclase.
Abstract: Anthrax toxin is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). These proteins individually cause no known physiological effects in animals but in pairs produce two toxic actions. Injection of PA with LF causes death of rats in 60 min, whereas PA with EF causes edema in the skin of rabbits and guinea pigs. The mechanisms of action of these proteins have not been determined. It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] produced by Bacillus anthracis in an inactive form. Activation occurs upon contact with a heat-stable eukaryotic cell material. The specific activity of the resulting adenylate cyclase nearly equals that of the most active known cyclase. In Chinese hamster ovary cells exposed to PA and EF, cAMP concentrations increase without a lag to values about 200-fold above normal, remain high in the continued presence of toxin, and decrease rapidly after its removal. The increase in cAMP is completely blocked by excess LF. It is suggested that PA interacts with cells to form a receptor system by which EF and perhaps LF gain access to the cytoplasm.
926 citations
TL;DR: It is likely that B. anthracis strains of temperature-sensitive plasmids which code for toxin structural or regulatory proteins are cured, like Pasteur vaccine strains, which were cured of their resident extrachromosomal gene pools by sequential passage of cultures.
Abstract: Large-molecular-weight plasmids were isolated from virulent and avirulent strains of Bacillus anthracis. Each strain contained a single plasmid species unique from the others with respect to molecular weight. Bacterial strains were cured of their resident extrachromosomal gene pools by sequential passage of cultures at 42.5 degrees C. Coincidental to the curing of plasmids was a loss of detectable lethal toxin and edema-producing activities and a dramatic decrease in lethal factor and protective antigen serological activities. The involvement of these plasmids in the production of toxin was firmly established by transformation of heat-passaged cells with plasmid DNA purified from the parent strain. The ability to produce parent strain levels of toxin was restored, and the plasmid DNA similar in molecular weight to that isolated from the parent was reisolated in all transformants examined. The exact role these plasmids play in the production of toxin remains to be elucidated. Two additional strains of B. anthracis, designated Pasteur vaccine strains, were examined for the ability to produce toxin and for the presence of plasmid DNA. Both strains were found to be nontoxigenic and contained no detectable plasmid elements. It is therefore likely that we, like Pasteur, cured B. anthracis strains of temperature-sensitive plasmids which code for toxin structural or regulatory proteins.
322 citations
TL;DR: The mouse model appears to be useful in studies on host resistance to anthrax and on the pathogenesis of the infection, especially when studies suggested that resistance to the Sterne strain is determined by a single dominant gene or gene complex.
Abstract: Animal species differ in their resistance both to infection by Bacillus anthracis and to anthrax toxin. A mouse model was developed to study the basis of the host differences and the pathogenesis of infection. When mice were infected with the virulent B. anthracis strain Vollum 1B, low 50% lethal dose (LD50) values (5 to 30 spores) were found for all 10 strains of inbred mice tested. However, analysis of time-to-death data revealed significant differences among the strains, which could be divided into three groups: most susceptible (A/J and DBA/2J); least susceptible (CBA/J, BALB/cJ, and C57BR/cdJ); and intermediate (the remaining five strains). In contrast, the mice were distinctly susceptible or resistant to lethal infection by the toxigenic, nonencapsulated Sterne vaccine strain. The LD50 for the susceptible A/J and DBA/2J mice was approximately 10(3) spores of the Sterne strain, whereas the remaining eight relatively resistant strains were killed only by 10(6) or more spores. F1 hybrid and backcross studies suggested that resistance to the Sterne strain is determined by a single dominant gene or gene complex. Mice lethally infected with B. anthracis showed an acute course of infection, characterized by extensive gelatinous edema and large concentrations of bacilli in the blood and organs (e.g., 10(9) CFU/g of spleen). The susceptibility of A/J and CBA/J mice to intravenously injected anthrax toxin components appeared to differ from their susceptibility to infection. The toxin LD50 values for both strains were similar. However, CBA/J mice died sooner than did A/J mice, with mean time to death of 0.9 and 3.7 days, respectively, in mice given 4 LD50 of toxin. The mouse model appears to be useful in studies on host resistance to anthrax and on the pathogenesis of the infection.
298 citations
TL;DR: This communication reports the data collected in a field study of a susceptible industrial population known to be chronically exposed to anthrax over a fouryear period.
Abstract: IN A SERIES of papers published from 1951-1955,'-" Wright and colleagues, reported on the development of an anthrax vaccine. This vaccine was shown to be an effective immunizing agent for laboratory animals and its safety for human use was demonstrated by the successful injection of 600 scientific personnel at Fort Detrick. Its value for human immunization could be established through a field study of a susceptible industrial population known to be chronically exposed to anthrax. This communication reports the data collected in such a study over a fouryear period.
253 citations
TL;DR: Data suggest that the galE S. typhi Ty21a oral vaccine strain, which presumably stimulates the local immune system in the intestine, may also serve as a useful carrier for other antigenic determinants to protect against different intestinal infections.
Abstract: Shigella sonnei, an intestinal pathogen, produces a characteristic form I cell surface antigen now known to be plasmid encoded. We considered that the GalE Salmonella typhi Ty21a oral vaccine strain, highly effective against typhoid, might be modified so as to be protective also against shigellosis due to S. sonnei. The plasmid responsible for form I antigen synthesis was therefore conjugally transferred to the galE S. typhi strain. Serological studies revealed that the derivative strain produces the form I antigen in addition to the normal S. typhi somatic antigens. Testing in mice demonstrated that the derivative form I galE S. typhi strain is protective against both S. sonnei and S. typhi challenges. These data suggest that the galE S. Ty21a oral vaccine strain, which presumably stimulates the local immune system in the intestine, may also serve as a useful carrier for other antigenic determinants to protect against different intestinal infections. Images
225 citations