Serious Adverse Events among Participants in the Centers for Disease Control and Prevention's Anthrax Vaccine and Antimicrobial Availability Program for Persons at Risk for Bioterrorism-Related Inhalational Anthrax

Tierney, Bruce C.; Martin, Stacey W.; Franzke, Laura; Marano, Nina; Reissman, Dori B.; Louchart, Randy D.; Goff, Joyce; Rosenstein, Nancy E.; Sever, John L.; McNeil, Michael M.

doi:10.1086/377738

Cited by 22 publications

(7 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since B. anthracis spores germinate asynchronously and often cause infection long after exposure, a prolonged period of prophylactic treatment with antibiotics is required (2,10,12,33). Because treatment regimens are lengthy, we investigated the protective effect of the human monoclonal antibody AVP-21D9, specific for B. anthracis PA, alone and in combination with ciprofloxacin using mouse, guinea pig, and rabbit models of intranasal challenge.…”

Section: Discussionmentioning

confidence: 99%

Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax

et al. 2006

View full text Add to dashboard Cite

Prevention of inhalation anthrax requires early and extended antibiotic therapy, and therefore, alternative treatment strategies are needed. We investigated whether a human monoclonal antibody (AVP-21D9) to protective antigen (PA) would protect mice, guinea pigs, and rabbits against anthrax. Control animals challenged with Bacillus anthracis Ames spores by the intranasal route died within 3 to 7 days. AVP-21D9 alone provided minimal protection against anthrax in the murine model, but its efficacy was notably better in guinea pigs. When Swiss-Webster mice, challenged with five 50% lethal doses (LD 50 s) of anthrax spores, were given a single 16.7-mg/kg of body weight AVP-21D9 antibody dose combined with ciprofloxacin (30 mg/kg/day for 6 days) 24 h after challenge, 100% of the mice were protected for more than 30 days, while ciprofloxacin or AVP-21D9 alone showed minimal protection. Similarly, when AVP-21D9 antibody (10 to 50 mg/kg) was combined with a low, nonprotective dose of ciprofloxacin (3.7 mg/kg/day) and administered to guinea pigs for 6 days, synergistic protection against anthrax was observed. In contrast, a single dose of AVP-21D9 antibody (1, 5, 10, or 20 mg/kg) but not 0.2 mg/kg alone completely protected rabbits against challenge with 100 LD 50 s of B. anthracis Ames spores, and 100% of the rabbits survived rechallenge. Further, administration of AVP-21D9 (10 mg/kg) to rabbits at 0, 6, and 12 h after challenge with anthrax spores resulted in 100% survival; however, delay of antibody treatment by 24 and 48 h reduced survival to 80% and 60%, respectively. Serological analysis of sera from various surviving animals 30 days postprimary infection showed development of a species-specific PA enzyme-linked immunosorbent assay antibody titer that correlated with protection against reinfection. Taken together, the effectiveness of human anti-PA antibody alone or in combination with low ciprofloxacin levels may provide the basis for an improved strategy for prophylaxis or treatment following inhalation anthrax infection.The severest form of anthrax results from inhalation of spores from Bacillus anthracis. The organism secretes three protein toxin components encoded by the genes cya, lef, and pag located on the pX01 plasmid (6,20,23). The virulence of B. anthracis is in part attributed to two separate bacterial proteins, edema factor (EF) (encoded by the cya gene) and lethal factor (LF) (encoded by the lef gene), both of which interact with protective antigen (PA) (encoded by the pag gene), a third protein that binds to receptors (4,16,28,30) on the host cell surface, forming edema toxin and lethal toxin (LeTx). EF, an 88.9-kDa protein, is a calmodulin-dependent adenylyl cyclase enzyme, while the 90.2-kDa LF is a Zn 2ϩ metalloprotease (6, 23). The 82.7-kDa receptor-binding PA is nicked by a furin-like protease produced by target cells and heptamerizes, forming binding sites for EF and LF. The membrane-bound holotoxin is then transported into the host cell by receptor-mediated endocytosis. Acidification of the e...

show abstract

Section: Discussionmentioning

confidence: 99%

Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Planning and responding to a bioterrorism event, including vaccinations and postexposure prophylaxis, is a challenging task. Vaccines for anthrax exist, ( 13,14 ) but in practice several obstacles are present in the form of potential adverse effects, ( 15,16 ) lengthy dose regimen requirements, ( 17 ) and widely varying perceptions of risk. ( 18 ) Furthermore, vaccination of the majority of populations in large urban areas would be impractical due to limited availability of prophylactics, and the costs associated with procuring and handling large supplies.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Modeling of Emergency Events: Assessing the Impact of Hypothetical Releases of Anthrax

2008

View full text Add to dashboard Cite

A modular system for source-to-dose-to-effect modeling analysis has been developed based on the modeling environment for total risk studies (MENTOR),(1) and applied to study the impacts of hypothetical atmospheric releases of anthrax spores. The system, MENTOR-2E (MENTOR for Emergency Events), provides mechanistically consistent analysis of inhalation exposures for various release scenarios, while allowing consideration of specific susceptible subpopulations (such as the elderly) at the resolution of individual census tracts. The MENTOR-2E application presented here includes atmospheric dispersion modeling, statistically representative samples of individuals along with corresponding activity patterns, and population-based dosimetry modeling that accounts for activity and physiological variability. Two hypothetical release scenarios were simulated: a 100 g release of weaponized B. anthracis over a period of (a) one hour and (b) 10 hours, and the impact of these releases on population in the State of New Jersey was studied. Results were compared with those from simplified modeling of population dynamics (location, activities, etc.), and atmospheric dispersion of anthrax spores. The comparisons showed that in the two release scenarios simulated, each major approximation resulted in an overestimation of the number of probable infections by a factor of 5 to 10; these overestimations can have significant public health implications when preparing for and responding effectively to an actual release. This is in addition to uncertainties in dose-response modeling, which result in an additional factor of 5 to 10 variation in estimated casualties. The MENTOR-2E system has been developed in a modular fashion so that improvements in individual modules can be readily made without impacting the other modules, and provides a first step toward the development of models that can be used in supporting real-time decision making.

show abstract

“…7 It has also been offered post-exposure in conjunction with antibiotics. 8 BioThrax™ is currently licensed for subcutaneous administration: three injections at two-week intervals followed by additional injections at six, twelve and eighteen months. After the six-dose series, yearly boosters are recommended.…”

Section: Introductionmentioning

confidence: 99%

Safety, Reactogenicity, and Immunogenicity of a Recombinant Protective Antigen Anthrax Vaccine Given to Healthy Adults

Campbell¹,

Clement²,

Wasserman³

et al. 2007

Human Vaccines

View full text Add to dashboard Cite

Background: Bacillus anthracis causes anthrax, a vaccine-preventable zoonotic disease that may follow intentional or unintentional exposure to its spores. Although an anthrax vaccine is currently licensed in the USA, better vaccines are desirable for both pre-and post-exposure prophylaxis.Methods: Healthy adults, aged 18-40 years, received anthrax immunization with either licensed Anthrax Vaccine Adsorbed (AVA, BioThrax™), or an experimental recombinant Protective Antigen vaccine (rPA) produced from an avirulent, non-spore-forming strain of B. anthracis at one of four doses (5, 25, 50 or 75 mg). Volunteers were followed for safety, reactogenicity, and immunogenicity.Results: rPA vaccine was well tolerated with a low rate of local or systemic reactions. Although antibody responses were poor following unadjuvanted rPA administration, 89 and 100% of volunteers who received Alhydrogel-adjuvanted rPA given intramuscularly had four-fold increases by enzyme-linked immunosorbent and toxin neutralization assays, respectively. Peak antibody responses to adjuvanted rPA given intramuscularly were equivalent to AVA, given either intramuscularly or subcutaneously, when measured by either assay.Conclusions: This recombinant Protective Antigen anthrax vaccine, when given with the adjuvant Alhydrogel to healthy adults in two intramuscular injections four weeks apart, is very well-tolerated and highly immunogenic.

show abstract

Serious Adverse Events among Participants in the Centers for Disease Control and Prevention's Anthrax Vaccine and Antimicrobial Availability Program for Persons at Risk for Bioterrorism-Related Inhalational Anthrax

Cited by 22 publications

References 14 publications

Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax

Human Monoclonal Anti-Protective Antigen Antibody Completely Protects Rabbits and Is Synergistic with Ciprofloxacin in Protecting Mice and Guinea Pigs against Inhalation Anthrax

Mechanistic Modeling of Emergency Events: Assessing the Impact of Hypothetical Releases of Anthrax

Safety, Reactogenicity, and Immunogenicity of a Recombinant Protective Antigen Anthrax Vaccine Given to Healthy Adults

Contact Info

Product

Resources

About