A recombinant 63-kDa form of Bacillus anthracis protective antigen produced in the yeast Saccharomyces cerevisiae provides protection in rabbit and primate inhalational challenge models of anthrax infection

Hepler, Robert; Kelly, Rosemarie; McNeely, Tessie; Fan, Hongxia; Losada, Maria C; George, Hugh A.; Woods, Andrea; Cope, Leslie D.; Bansal, Alka; Cook, James C.

doi:10.1016/j.vaccine.2005.10.018

Cited by 21 publications

(11 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This vaccine (AVA) was used to immunize individuals at high risk of occupational exposure. More recently, investigators have evaluated vaccines composed of a recombinant form of the PA in rhesus macaques (Hepler et al 2006;Phipps et al 2004;Williamson et al 2005); they found that the animals were fully protected against a lethal dose of aerosolized bacteria and that protection correlated significantly with neutralizing antibodies, which also conferred passive immunity to B. anthracis challenge of naïve macaques. A DNA vaccine for anthrax is also efficacious in macaques (Riemenschneider et al 2003).…”

Section: Anthrax (Bacillus Anthracis)mentioning

confidence: 99%

Macaque Models of Human Infectious Disease

Gardner¹,

Luciw²

2008

ILAR Journal

174

133

View full text Add to dashboard Cite

Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease.

show abstract

Section: Anthrax (Bacillus Anthracis)mentioning

confidence: 99%

Macaque Models of Human Infectious Disease

Gardner¹,

Luciw²

2008

ILAR Journal

174

133

View full text Add to dashboard Cite

show abstract

“…The pathological changes in both NHPs and rabbits following aerosol exposure to B. anthracis spores resembles that associated with human inhalation anthrax (20,72,80). Vaccination with AVA or rPA was protective against an aerosol exposure to spores in both NHP and New Zealand White (NZW) rabbits, and the development of anti-PA antibodies correlated with protection (17,25,28,43,44,58,76). However, because PA is required for both toxins to function, it is unclear whether the protective effect of anti-PA antibody is primarily due to the neutralization of LT and/or ET.…”

mentioning

confidence: 99%

Expression of either Lethal Toxin or Edema Toxin by Bacillus anthracis Is Sufficient for Virulence in a Rabbit Model of Inhalational Anthrax

et al. 2012

View full text Add to dashboard Cite

ABSTRACTThe development of therapeutics against biothreats requires that we understand the pathogenesis of the disease in relevant animal models. The rabbit model of inhalational anthrax is an important tool in the assessment of potential therapeutics againstBacillus anthracis. We investigated the roles ofB. anthraciscapsule and toxins in the pathogenesis of inhalational anthrax in rabbits by comparing infection with the Ames strain versus isogenic mutants with deletions of the genes for the capsule operon (capBCADE), lethal factor (lef), edema factor (cya), or protective antigen (pagA). The absence of capsule or protective antigen (PA) resulted in complete avirulence, while the presence of either edema toxin or lethal toxin plus capsule resulted in lethality. The absence of toxin did not influence the ability ofB. anthracisto traffic to draining lymph nodes, but systemic dissemination required the presence of at least one of the toxins. Histopathology studies demonstrated minimal differences among lethal wild-type and single toxin mutant strains. When rabbits were coinfected with the Ames strain and the PA− mutant strain, the toxin produced by the Ames strain was not able to promote dissemination of the PA− mutant, suggesting that toxigenic action occurs in close proximity to secreting bacteria. Taken together, these findings suggest that a major role for toxins in the pathogenesis of anthrax is to enable the organism to overcome innate host effector mechanisms locally and that much of the damage during the later stages of infection is due to the interactions of the host with the massive bacterial burden.

show abstract

“…The yeast S. cerevisiae is one of the organisms widely used in industrial microbiology for the production not only of ethanol but of recombinant proteins, 17) bioactive substances, 18) and vaccines. 19) S. cerevisiae is also nonpathogenic, and, given its long history of application in the production of food and alcoholic beverages, it has been classified as a GRAS (generally regarded as safe) organism. 20) In addition, the well-established fermentation and process technology for large-scale production using S. cerevisiae make this organism attractive for use as a fermenter.…”

mentioning

confidence: 99%

Metabolic Engineering ofSaccharomyces cerevisiaeProducing Nicotianamine: Potential for Industrial Biosynthesis of a Novel Antihypertensive Substrate

Wada¹,

Kobayashi²,

Takahashi³

et al. 2006

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

Nicotianamine (NA), a metal chelator, is ubiquitous in higher plants. In humans, NA inhibits angiotensin I-converting enzyme (ACE), and consequently reduces high blood pressure. Nicotianamine is synthesized from the trimerization of S-adenosylmethionine (SAM) by NA synthase (NAS). Here, we aimed to produce large amounts of NA fermentatively by introducing the Arabidopsis AtNAS2 gene into Saccharomyces cerevisiae strain SCY4. This strain can accumulate up to 100 times the usual amount of SAM, and this is considered desirable for overproduction of NA. Nicotianamine was produced in the engineered yeast, and the NA level increased with incubation time until the stationary phase. The maximum concentration of intracellular NA obtained was 766+/-33 microg/g wet weight. Successful production of NA in S. cerevisiae should pave the way for industrial production of this novel antihypertensive substrate.

show abstract

A recombinant 63-kDa form of Bacillus anthracis protective antigen produced in the yeast Saccharomyces cerevisiae provides protection in rabbit and primate inhalational challenge models of anthrax infection

Cited by 21 publications

References 71 publications

Macaque Models of Human Infectious Disease

Macaque Models of Human Infectious Disease

Expression of either Lethal Toxin or Edema Toxin by Bacillus anthracis Is Sufficient for Virulence in a Rabbit Model of Inhalational Anthrax

Metabolic Engineering ofSaccharomyces cerevisiaeProducing Nicotianamine: Potential for Industrial Biosynthesis of a Novel Antihypertensive Substrate

Contact Info

Product

Resources

About