Protective-antigen (PA) based anthrax vaccines confer protection against inhalation anthrax by precluding the establishment of a systemic infection

Merkel, Tod J.; Perera, Pin-Yu; Lee, Gloria M.; Verma, Anita; Hiroi, Toyoko; Yokote, Hiroyuki; Waldmann, Thomas A.; Perera, Liyanage P.

doi:10.4161/hv.25337

Cited by 9 publications

(4 citation statements)

References 21 publications

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“…In New Zealand White rabbits, even 1:16 diluted AVA vaccination results in 96% survival, compared to 0% of the control (34). Finally, it was seen in mice, specifically the A/J strain used in this study, that vaccination with AVA induces 100% survival when challenged with 20ϫ LD 50 inhalational Sterne strain 7702 spores (35). One concern, however, is that AVA is ineffective in protecting rabbits against nontoxigenic strains of Turbo 15; Sartorious).…”

Section: Discussionmentioning

confidence: 60%

Progress towards the Development of a NEAT Vaccine for Anthrax II: Immunogen Specificity and Alum Effectiveness in an Inhalational Model

et al. 2020

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Bacillus anthracis is the causative agent of anthrax disease, presents with high mortality, and has been at the center of bioweapon efforts. The only currently U.S. FDA-approved vaccine to prevent anthrax in humans is anthrax vaccine adsorbed (AVA), which is protective in several animal models and induces neutralizing antibodies against protective antigen (PA), the cell-binding component of anthrax toxin. However, AVA requires a five-course regimen to induce immunity, along with an annual booster, and is composed of undefined culture supernatants from a PA-secreting strain. In addition, it appears to be ineffective against strains that lack anthrax toxin. Here, we investigated a vaccine formulation consisting of recombinant proteins from a surface-localized heme transport system containing near-iron transporter (NEAT) domains and its efficacy as a vaccine for anthrax disease. The cocktail of five NEAT domains was protective against a lethal challenge of inhaled bacillus spores at 3 and 28 weeks after vaccination. The reduction of the formulation to three NEATs (IsdX1, IsdX2, and Bslk) was as effective as a five-NEAT domain cocktail. The adjuvant alum, approved for use in humans, was as protective as Freund’s Adjuvant, and protective vaccination correlated with increased anti-NEAT antibody reactivity and reduced bacterial levels in organs. Finally, the passive transfer of anti-NEAT antisera reduced mortality and disease severity, suggesting the protective component is comprised of antibodies. Collectively, these results provide evidence that a vaccine based upon recombinant NEAT proteins should be considered in the development of a next-generation anthrax vaccine.

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Section: Discussionmentioning

confidence: 60%

Progress towards the Development of a NEAT Vaccine for Anthrax II: Immunogen Specificity and Alum Effectiveness in an Inhalational Model

et al. 2020

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“…PA is considered an important antigen in B. anthrax development. Immunity against an anthrax infection requires a sufficient humoral response to PA [47,48]. Anti-PA antibodies have been demonstrated to block the early stages of spore infection and neutralize anthrax toxin activity [49].…”

Section: Discussionmentioning

confidence: 99%

Pathogenicity and Genomic Characterization of a Novel Genospecies, Bacillus shihchuchen, of the Bacillus cereus Group Isolated from Chinese Softshell Turtle (Pelodiscus sinensis)

Cheng

Byadgi

Tsai

et al. 2023

IJMS

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The Chinese softshell turtle (CST; Pelodiscus sinensis) is a freshwater aquaculture species of substantial economic importance that is commercially farmed across Asia, particularly in Taiwan. Although diseases caused by the Bacillus cereus group (Bcg) pose a major threat to commercial CST farming systems, information regarding its pathogenicity and genome remains limited. Here, we investigated the pathogenicity of Bcg strains isolated in a previous study and performed whole-genome sequencing. Pathogenicity analysis indicated that QF108-045 isolated from CSTs caused the highest mortality rate, and whole-genome sequencing revealed that it was an independent group distinct from other known Bcg genospecies. The average nucleotide identity compared to other known Bcg genospecies was below 95%, suggesting that QF108-045 belongs to a new genospecies, which we named Bacillus shihchuchen. Furthermore, genes annotation revealed the presence of anthrax toxins, such as edema factor and protective antigen, in QF108-045. Therefore, the biovar anthracis was assigned, and the full name of QF108-045 was Bacillus shihchuchen biovar anthracis. In addition to possessing multiple drug-resistant genes, QF108-045 demonstrated resistance to various types of antibiotics, including penicillins (amoxicillin and ampicillin), cephalosporins (ceftifour, cephalexin, and cephazolin), and polypeptides, such as vancomycin.

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“…11 Two reasons for highly lethal nature (50%-90%) of inhalation form have been suggested as follows: toxemia model and overwhelming bacteremia leading to severe sepsis. 12,13 Two cases of anthrax were reported in heroin users in Scotland, which were subsequently spread into England and Germany. 14 An inhalation form with an unknown source was diagnosed in a patient in the United States.…”

Section: Contextmentioning

confidence: 99%

The Anthrax Disease in Iran From 2000 to 2016: The Predominance of Cutaneous and Gastrointestinal Form

Ghasemian¹,

Nojoomi²,

Rajabi-Vardanjani³

2017

Int J Enteric Pathog

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Context: Anthrax is a zoonotic and occupational disease caused by bacterium Bacillus anthracis. The agent produces spores which persist in the environment for years. This review assessed previous reports on anthrax disease in Iran from 2000 to 2016. Evidence acquisition: The reports of anthrax from 2000 to 2016 were reviewed. The keywords "Bacillus anthracis", "Anthrax", "clinical signs", "Iran" and "zoonosis" were investigated in the searching databases such as "Google Scholar", "Google", "PubMed" and other sites. The reports of soil isolation and spores from environments were excluded. However, the clinical outcome of the cases, history of animal exposure, wool contaminations and meat in slaughterhouses were included. Results of Persian reports were also included in this review. Data were analyzed using Excel and GraphPad Prism version 6.1. The standardized mean difference (SMD) was used for data analysis.. Overall, 768 cases of anthrax were found in human, sheep, goats and cattle. Six hundred of the human cases aged between 2.5 and 71 years old were included. Four-hundred ten (68.33%) patients were male (mean age=28.1 ± 1.5) and 190 (31.66%) patients were female (mean age = 17±1.5). Clinical manifestations in patients were mostly in 2 cutaneous (56.6%) and gastrointestinal (42.83%) forms. Sporadic anthrax outbreaks occurred in the country in 2007, 2008 and 2011. No molecular typing has been performed for B. anthracis strains countrywide. The virulence factors encoded by the genes located on plasmids pXO1 and pXO2 were detected in various areas with high prevalence. Conclusion: Cutaneous and gastrointestinal anthrax are 2 main manifestations of the disease in Iran. Male patients were significantly more infected. Although rare, anthrax continues to be a dreadful consequence of herds or soil exposure and consumption of undercooked meat of infected animals. Education plans and proper animal vaccination plans with the consideration of virulence factors are helpful for the prevention of the disease.

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Protective-antigen (PA) based anthrax vaccines confer protection against inhalation anthrax by precluding the establishment of a systemic infection

Cited by 9 publications

References 21 publications

Progress towards the Development of a NEAT Vaccine for Anthrax II: Immunogen Specificity and Alum Effectiveness in an Inhalational Model

Progress towards the Development of a NEAT Vaccine for Anthrax II: Immunogen Specificity and Alum Effectiveness in an Inhalational Model

Pathogenicity and Genomic Characterization of a Novel Genospecies, Bacillus shihchuchen, of the Bacillus cereus Group Isolated from Chinese Softshell Turtle (Pelodiscus sinensis)

The Anthrax Disease in Iran From 2000 to 2016: The Predominance of Cutaneous and Gastrointestinal Form

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