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J. Barth

Bio: J. Barth is an academic researcher from United States Army Medical Research Institute of Infectious Diseases. The author has contributed to research in topics: Anthrax Vaccine Adsorbed & Bacillus anthracis. The author has an hindex of 2, co-authored 2 publications receiving 349 citations.

Papers
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Journal ArticleDOI
14 Sep 2001-Vaccine
TL;DR: A serological correlate of vaccine-induced immunity was identified in the rabbit model of inhalational anthrax and antibody levels to PA at both 6 and 10 weeks were significant predictors of survival.

267 citations

Journal ArticleDOI
TL;DR: In these studies, the licensed anthrax vaccine adsorbed (AVA) in rabbits was used and the quantity of anti‐PA antibodies with protective immunity in the guinea pig model for anthrax and various vaccine formulations have failed.
Abstract: fA serological correlate of vaccine-induced immunity was identified in the rabbit model of inhalational anthrax. Animals were inoculated intramuscularly at 0 and 4 weeks with varying doses of Anthrax Vaccine Adsorbed (AVA) ranging from a human dose to a 1:256 dilution in phosphate-buffered saline (PBS). At 6 and 10 weeks, both the quantitative anti-protective antigen (PA) IgG ELISA and the toxin-neutralizing antibody (TNA) assays were used to measure antibody levels to PA. Rabbits were aerosol-challenged at 10 weeks with a lethal dose (84-133 LD,,) of Bacillus anthracis spores. All the rabbits that received the undiluted and 1:4 dilution of vaccine survived, whereas those receiving the higher dilutions of vaccine (1:16, 154 and 1:256) had deaths in their groups. ~esults showed that antibody levels to PA at both 6 and 10 weeks were significant (P < 0.0001) predictors of survival. Published by Elsevier Science Ltd. Keynlords: Anthrax; Baci//us anfltracis; Serological correlate

91 citations


Cited by
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Journal ArticleDOI
TL;DR: This paper attempts to summarize current knowledge about immune responses to vaccines that correlate with protection, finding some vaccines have no true correlates, but only useful surrogates, for an unknown protective response.
Abstract: This paper attempts to summarize current knowledge about immune responses to vaccines that correlate with protection. Although the immune system is redundant, almost all current vaccines work through antibodies in serum or on mucosa that block infection or bacteremia/viremia and thus provide a correlate of protection. The functional characteristics of antibodies, as well as quantity, are important. Antibody may be highly correlated with protection or synergistic with other functions. Immune memory is a critical correlate: effector memory for short-incubation diseases and central memory for long-incubation diseases. Cellular immunity acts to kill or suppress intracellular pathogens and may also synergize with antibody. For some vaccines, we have no true correlates, but only useful surrogates, for an unknown protective response.

1,350 citations

Journal ArticleDOI
01 May 2002-JAMA
TL;DR: This revised consensus statement presents new information based on the analysis of the anthrax attacks of 2001, including developments in the investigation of the Anthrax Attacks of 2001; important symptoms, signs, and laboratory studies; new diagnostic clues that may help future recognition of this disease; updated antibiotic therapeutic considerations; and judgments about environmental surveillance and decontamination.
Abstract: ObjectiveTo review and update consensus-based recommendations for medical and public health professionals following a Bacillus anthracis attack against a civilian population.ParticipantsThe working group included 23 experts from academic medical centers, research organizations, and governmental, military, public health, and emergency management institutions and agencies.EvidenceMEDLINE databases were searched from January 1966 to January 2002, using the Medical Subject Headings anthrax, Bacillus anthracis, biological weapon, biological terrorism, biological warfare, and biowarfare. Reference review identified work published before 1966. Participants identified unpublished sources.Consensus ProcessThe first draft synthesized the gathered information. Written comments were incorporated into subsequent drafts. The final statement incorporated all relevant evidence from the search along with consensus recommendations.ConclusionsSpecific recommendations include diagnosis of anthrax infection, indications for vaccination, therapy, postexposure prophylaxis, decontamination of the environment, and suggested research. This revised consensus statement presents new information based on the analysis of the anthrax attacks of 2001, including developments in the investigation of the anthrax attacks of 2001; important symptoms, signs, and laboratory studies; new diagnostic clues that may help future recognition of this disease; current anthrax vaccine information; updated antibiotic therapeutic considerations; and judgments about environmental surveillance and decontamination.

948 citations

Journal ArticleDOI
TL;DR: Correlates of protection after vaccination are sometimes absolute quantities but often are relative, such that most infections are prevented at a particular level of response but some will occur above that level because of a large challenge dose or deficient host factors.
Abstract: The immune system is redundant, and B and T cells collaborate. However, almost all current vaccines work through induction of antibodies in serum or on mucosa that block infection or interfere with microbial invasion of the bloodstream. To protect, antibodies must be functional in the sense of neutralization or opsonophagocytosis. Correlates of protection after vaccination are sometimes absolute quantities but often are relative, such that most infections are prevented at a particular level of response but some will occur above that level because of a large challenge dose or deficient host factors. There may be >1 correlate of protection for a disease, which we term "cocorrelates." Either effector or central memory may correlate with protection. Cell-mediated immunity also may operate as a correlate or cocorrelate of protection against disease, rather than against infection. In situations where the true correlate of protection is unknown or difficult to measure, surrogate tests (usually antibody measurements) must suffice as predictors of protection by vaccines. Examples of each circumstance are given.

741 citations

Journal ArticleDOI
TL;DR: This review comprehensively surveys the literature and discusses the similarities and distinct differences between each Clostridium and Bacillus binary toxin in terms of their biochemistry, biology, genetics, structure, and applications in science and medicine.
Abstract: Certain pathogenic species of Bacillus and Clostridium have developed unique methods for intoxicating cells that employ the classic enzymatic “A-B” paradigm for protein toxins. The binary toxins produced by B. anthracis, B. cereus, C. botulinum, C. difficile, C. perfringens, and C. spiroforme consist of components not physically associated in solution that are linked to various diseases in humans, animals, or insects. The “B” components are synthesized as precursors that are subsequently activated by serine-type proteases on the targeted cell surface and/or in solution. Following release of a 20-kDa N-terminal peptide, the activated “B” components form homoheptameric rings that subsequently dock with an “A” component(s) on the cell surface. By following an acidified endosomal route and translocation into the cytosol, “A” molecules disable a cell (and host organism) via disruption of the actin cytoskeleton, increasing intracellular levels of cyclic AMP, or inactivation of signaling pathways linked to mitogen-activated protein kinase kinases. Recently, B. anthracis has gleaned much notoriety as a biowarfare/bioterrorism agent, and of primary interest has been the edema and lethal toxins, their role in anthrax, as well as the development of efficacious vaccines and therapeutics targeting these virulence factors and ultimately B. anthracis. This review comprehensively surveys the literature and discusses the similarities, as well as distinct differences, between each Clostridium and Bacillus binary toxin in terms of their biochemistry, biology, genetics, structure, and applications in science and medicine. The information may foster future studies that aid novel vaccine and drug development, as well as a better understanding of a conserved intoxication process utilized by various gram-positive, spore-forming bacteria.

396 citations

Journal ArticleDOI
TL;DR: In vitro, post-challenge protection of macrophages from the action of the holotoxin correlated with the Kd of the scFv variants, and strong correlations among antibody construct affinity, serum half-life, and protection were also observed in a rat model of toxin challenge.
Abstract: The tripartite toxin produced by Bacillus anthracis is the key determinant in the etiology of anthrax. We have engineered a panel of toxin-neutralizing antibodies, including single-chain variable fragments (scFvs) and scFvs fused to a human constant κ domain (scAbs), that bind to the protective antigen subunit of the toxin with equilibrium dissociation constants (Kd) between 63 nM and 0.25 nM. The entire antibody panel showed high serum, thermal, and denaturant stability. In vitro, post-challenge protection of macrophages from the action of the holotoxin correlated with the K d of the scFv variants. Strong correlations among antibody construct affinity, serum half-life, and protection were also observed in a rat model of toxin challenge. High-affinity toxinneutralizing antibodies may be of therapeutic value for alleviating the symptoms of anthrax toxin in infected individuals and for medium-term prophylaxis to infection.

322 citations