Anthrax vaccine design: strategies to achieve comprehensive protection against spore, bacillus, and toxin

Wang, Julia Y.; Roehrl, Michael H.

doi:10.1186/1476-9433-4-4

Cited by 68 publications

(38 citation statements)

References 79 publications

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“…It is thought that one of the functions of the capsule of pathogenic bacteria is to protect against the host immune system, perhaps by inhibiting phagocytosis (84). The poly-␥-D-glutamic acid (PGA) capsule of B. anthracis is a poor immunogen; however, coupling PGA to a strong immunogen, including protective antigen, leads to anticapsule antibodies that promote the killing and clearance of bacilli (25,85,86).…”

Section: Discussionmentioning

confidence: 99%

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

et al. 2016

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Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S.-licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed [AVA]) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multishot regimen, recommended boosters, and potential for adverse reactions. Improving next-generation anthrax vaccines is important to safeguard citizens and the military. Here, we report that vaccination with recombinant forms of a conserved domain (near-iron transporter [NEAT]), common in Gram-positive pathogens, elicits protection in a murine model of B. anthracis infection. Protection was observed with both Freund's and alum adjuvants, given subcutaneously and intramuscularly, respectively, with a mixed composite of NEATs. Protection correlated with an antibody response against the NEAT domains and a decrease in the numbers of bacteria in major organs. Anti-NEAT antibodies promote opsonophagocytosis of bacilli by alveolar macrophages. To guide the development of inactive and safe NEAT antigens, we also report the crystal structure of one of the NEAT domains (Hal) and identify critical residues mediating its heme-binding and acquisition activity. These results indicate that we should consider NEAT proteins in the development of an improved antianthrax vaccine.

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Section: Discussionmentioning

confidence: 99%

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

et al. 2016

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“…The endospores are not only transmittable easily to humans but also resistant to harsh environments, 29 all of which have made the anthrax endospores a potential BWMD. 30 Once inhaled, the endospores are engulfed either by host defense cells where the spores germinate and assume vegetative forms. The vegetative bacterial cells are disseminated, causing septicemia and producing virulence factors.…”

Section: Discussionmentioning

confidence: 99%

Detection of anthrax lef with DNA-based photonic crystal sensors

et al. 2011

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Bacillus anthracis has posed a threat of becoming biological weapons of mass destruction due to its virulence factors encoded by the plasmid-borne genes, such as lef for lethal factor. We report the development of a fast and sensitive anthrax DNA biosensor based on a photonic crystal structure used in a total-internal-reflection configuration. For the detection of the lef gene, a single-stranded DNA lef probe was biotinylated and immobilized onto the sensor via biotin-streptavidin interactions. A positive control, lef-com, was the complementary strand of the probe, while a negative control was an unrelated single-stranded DNA fragment from the 16S rRNA gene of Acinetobacter baumannii. After addition of the biotinylated lef probe onto the sensor, significant changes in the resonance wavelength of the sensor were observed, resulting from binding of the probe to streptavidin on the sensor. The addition of lef-com led to another significant increase as a result of hybridization between the two DNA strands. The detection sensitivity for the target DNA reached as low as 0.1 nM. In contrast, adding the unrelated DNAs did not cause an obvious shift in the resonant wavelength. These results demonstrate that detection of the anthrax lef by the photonic crystal structure in a total-internal-reflection sensor is highly specific and sensitive.

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“…Antibody responses against PA target and block the toxemia that is a necessary prerequisite of vegetative cell growth and bacteremia. Vaccines comprising additional B. anthracis specific antigens have been proposed as improvements to PA‐only formulations as they have the potential to target inclusively the toxemia and the vegetative cell or infectious spore 9–11. Recently described polysaccharides and glycoproteins of B. anthracis offer exciting new targets for these vaccine formulations and also for the development of improved diagnostics for B. anthracis .…”

Section: Methodsmentioning

confidence: 99%

Chemical Synthesis and Immunological Properties of Oligosaccharides Derived from the Vegetative Cell Wall of Bacillus anthracis

Vasan¹,

Rauvolfová²,

Wolfert³

et al. 2008

ChemBioChem

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Bacillus anthracis vaccine candidate: Sera of rabbits exposed to live and irradiated-killed spores of B. anthracis Sterne 34F2 or immunized with B. anthracis polysaccharide conjugated to KLH elicited antibodies that recognize isolated polysaccharide and two synthetic trisaccharides providing a proof-of-concept step in the development of vegetative and spore-specific reagents for detection and targeting of non-protein structures of B. anthracis.

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Anthrax vaccine design: strategies to achieve comprehensive protection against spore, bacillus, and toxin

Cited by 68 publications

References 79 publications

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

Detection of anthrax lef with DNA-based photonic crystal sensors

Chemical Synthesis and Immunological Properties of Oligosaccharides Derived from the Vegetative Cell Wall of Bacillus anthracis

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