Modeling low-dose mortality and disease incubation period of inhalational anthrax in the rabbit

Gutting, Bradford W.; Marchette, David J.; Sherwood, Robert; Andrews, Gordon; Director-Myska, Alison E.; Channel, Stephen R.; Wolfe, Daniel; Berger, Alan E.; Mackie, Ryan S.; Watson, Brent J.; Rukhin, Andrey

doi:10.1016/j.jtbi.2013.03.020

Cited by 12 publications

(53 citation statements)

References 37 publications

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“…The reported deposition fractions varied between 1.33% and 4.93%, which were somewhat lower than model predictions of 7.62%. However, as discussed by Kabilan et al (2016), deposition measurements may have been underestimated due to epithelial cell internalization of the deposited particles in the Gutting (2013) study and the inability of Broncho-alveolar lavage to wash out all deposited particles in the Gutting et al (2012) study.…”

Section: Resultsmentioning

confidence: 97%

“…This restriction does not impose a limitation on deposition prediction of anthrax spores, which are around one-micrometer in diameter (Gutting et al, 2012, 2013). In this study, deposition fractions and exposure concentrations were calculated for particle diameters 0.1 μm and above in accordance with URT deposition data.…”

Section: Resultsmentioning

confidence: 99%

“…Gutting et al (2012) and (2013) exposed New Zealand white rabbits to B. anthracis spores with mass median diameter of1 μm ±0.3 μm and measured the lung content of anthrax spores. Table II lists measured and predicted deposition fractions.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, single B. anthracis spore diameter was measured to be sub-micrometer or larger (Carrera et al, 2007; Gutting et al, 2012, 2013). Thus, no attempt was made in this study to model the deposition of ultrafine particles by Brownian diffusion in the URT of rabbits.…”

Section: Methodsmentioning

confidence: 99%

“…In particular, rabbits have often been selected as the animal of choice to study anthrax inhalation (Gutting et al, 2012; Twenhafel, 2010; Yee et al, 2010; Zaucha et al, 1998) in part because they are cheaper than nonhuman primates and easier to house and handle. Consequently, inhalation studies in rabbits were conducted to develop risk models (Gutting et al, 2012, 2013) - expressed as statistical relationships between the deposited dose and mortality, defined as lethal dose for 50% of the population (or LD 50 ). Risk models in rabbits can be readily extended to humans if complemented by exposure-dose models both in humans and rabbits.…”

Section: Introductionmentioning

confidence: 99%

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Development of a Zealand white rabbit deposition model to study inhalation anthrax

Asgharian

Price

Kabilan

et al. 2016

Inhalation Toxicology

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Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Development of a Zealand white rabbit deposition model to study inhalation anthrax

Asgharian

Price

Kabilan

et al. 2016

Inhalation Toxicology

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Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

Kabilan

Suffield

Recknagle

et al. 2016

Journal of Aerosol Science

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Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation

Renukaradhya

Narasimhan

Mallapragada

2015

Journal of Controlled Release

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Vaccine development has had a huge impact on human health. However, there is a significant need to develop efficacious vaccines for several existing as well as emerging respiratory infectious diseases. Several challenges need to be overcome to develop efficacious vaccines with translational potential. This review focuses on two aspects to overcome some barriers – 1) the development of nanoparticle-based vaccines, and 2) the choice of suitable animal models for respiratory infectious diseases that will allow for translation. Nanoparticle-based vaccines, including subunit vaccines involving synthetic and/or natural polymeric adjuvants and carriers, as well as those based on virus-like particles offer several key advantages to help overcome the barriers to effective vaccine development. These include the ability to deliver combinations of antigens, target the vaccine formulation to specific immune cells, enable cross-protection against divergent strains, act as adjuvants or immunomodulators, allow for sustained release of antigen, enable single dose delivery, and potentially obviate the cold chain. While mouse models have provided several important insights into the mechanisms of infectious diseases, they are often a limiting step in translation of new vaccines to the clinic. An overview of different animal models involved in vaccine research for respiratory infections, with advantages and disadvantages of each model, are discussed. Taken together, advances in nanotechnology, combined with the right animal models for evaluating vaccine efficacy, has the potential to revolutionize vaccine development for respiratory infections.

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Modeling low-dose mortality and disease incubation period of inhalational anthrax in the rabbit

Cited by 12 publications

References 37 publications

Development of a Zealand white rabbit deposition model to study inhalation anthrax

Development of a Zealand white rabbit deposition model to study inhalation anthrax

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

Respiratory nanoparticle-based vaccines and challenges associated with animal models and translation

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