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

2006 ◽  
Vol 74 (2) ◽  
pp. 1016-1024 ◽  
Author(s):  
Johnny W. Peterson ◽  
Jason E. Comer ◽  
David M. Noffsinger ◽  
Autumn Wenglikowski ◽  
Kristin G. Walberg ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Protective Antigen ◽  
Human Monoclonal Antibody ◽  
Treatment Strategies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antibody Treatment ◽  
Inhalation Anthrax ◽  
Anthrax Infection ◽  
Anthrax Spores ◽  
Species Specific

ABSTRACT 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 (LD50s) 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 LD50s 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.

scholarly journals Human Monoclonal Antibody AVP-21D9 to Protective Antigen Reduces Dissemination of the Bacillus anthracis Ames Strain from the Lungs in a Rabbit Model

2007 ◽  
Vol 75 (7) ◽  
pp. 3414-3424 ◽  
Author(s):  
Johnny W. Peterson ◽  
Jason E. Comer ◽  
Wallace B. Baze ◽  
David M. Noffsinger ◽  
Autumn Wenglikowski ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Human Monoclonal Antibody ◽  
Rabbit Model ◽  
Concomitant Treatment ◽  
Dependent Manner ◽  
Lethal Challenge ◽  
Tissue Sections ◽  
Inhalation Anthrax

ABSTRACT Dutch-belted and New Zealand White rabbits were passively immunized with AVP-21D9, a human monoclonal antibody to protective antigen (PA), at the time of Bacillus anthracis spore challenge using either nasal instillation or aerosol challenge techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit strains against lethal infection with Bacillus anthracis Ames spores, regardless of the inoculation method. Further, all but one of the passively immunized animals (23/24) were completely resistant to rechallenge with spores by either respiratory challenge method at 5 weeks after primary challenge. Analysis of the sera at 5 weeks after primary challenge showed that residual human anti-PA levels decreased by 85 to 95%, but low titers of rabbit-specific anti-PA titers were also measured. Both sources of anti-PA could have contributed to protection from rechallenge. In a subsequent study, bacteriological and histopathology analyses revealed that B. anthracis disseminated to the bloodstream in some naïve animals as early as 24 h postchallenge and increased in frequency with time. AVP-21D9 significantly reduced the dissemination of the bacteria to the bloodstream and to various organs following infection. Examination of tissue sections from infected control animals, stained with hematoxylin-eosin and the Gram stain, showed edema and/or hemorrhage in the lungs and the presence of bacteria in mediastinal lymph nodes, with necrosis and inflammation. Tissue sections from infected rabbits dosed with AVP-21D9 appeared comparable to corresponding tissues from uninfected animals despite lethal challenge with B. anthracis Ames spores. Concomitant treatment with AVP-21D9 at the time of challenge conferred complete protection in the rabbit inhalation anthrax model. Early treatment increased the efficacy progressively and in a dose-dependent manner. Thus, AVP-21D9 could offer an adjunct or alternative clinical treatment regimen against inhalation anthrax.

scholarly journals Evaluation of Intravenous Anthrax Immune Globulin for Treatment of Inhalation Anthrax

2013 ◽  
Vol 57 (11) ◽  
pp. 5684-5692 ◽  
Author(s):  
Nutan Mytle ◽  
Robert J. Hopkins ◽  
Nina V. Malkevich ◽  
Subhendu Basu ◽  
Gabriel T. Meister ◽  
...  
Keyword(s):  
Clinical Study ◽  
Protective Antigen ◽  
Healthy Human ◽  
Content Type ◽  
Lower Survival Rate ◽  
Elimination Half ◽  
Human Volunteers ◽  
Inhalation Anthrax ◽  
Anthrax Spores ◽  
Anthrax Toxins

ABSTRACTBacillus anthracistoxins can be neutralized by antibodies against protective antigen (PA), a component of anthrax toxins. Anthrivig (human anthrax immunoglobulin), also known as AIGIV, derived from plasma of humans immunized with BioThrax (anthrax vaccine adsorbed), is under development for the treatment of toxemia following exposure to anthrax spores. The pharmacokinetics (PK) of AIGIV was assessed in naive animals and healthy human volunteers, and the efficacy of AIGIV was assessed in animals exposed via inhalation to aerosolizedB. anthracisspores. In the clinical study, safety, tolerability, and PK were evaluated in three dose cohorts (3.5, 7.1, and 14.2 mg/kg of body weight of anti-PA IgG) with 30 volunteers per cohort. The elimination half-life of AIGIV in rabbits, nonhuman primates (NHPs), and humans following intravenous infusion was estimated to be approximately 4, 12, and 24 days, respectively, and dose proportionality was observed. In a time-based treatment study, AIGIV protected 89 to 100% of animals when administered 12 h postexposure; however, a lower survival rate of 39% was observed when animals were treated 24 h postexposure, underscoring the need for early intervention. In a separate set of studies, animals were treated on an individual basis upon detection of a clinical sign or biomarker of disease, namely, a significant increase in body temperature (SIBT) in rabbits and presence of PA in the serum of NHPs. In these trigger-based intervention studies, AIGIV induced up to 75% survival in rabbits depending on the dose and severity of toxemia at the time of treatment. In NHPs, up to 33% survival was observed in AIGIV-treated animals. (The clinical study has been registered atClinicalTrials.govunder registration no. NCT00845650.)

scholarly journals Anthrax Spores Make an Essential Contribution to Vaccine Efficacy

2002 ◽  
Vol 70 (2) ◽  
pp. 661-664 ◽  
Author(s):  
Fabien Brossier ◽  
Martine Levy ◽  
Michèle Mock
Keyword(s):  
Guinea Pigs ◽  
Protective Antigen ◽  
Humoral Response ◽  
Anthrax Toxin ◽  
Experimental Animals ◽  
Challenge Strain ◽  
Anthrax Spores ◽  
Acellular Vaccines ◽  
Essential Contribution ◽  
Anthrax Vaccines

ABSTRACT Anthrax is caused by Bacillus anthracis, a gram-positive spore-forming bacterium. Septicemia and toxemia rapidly lead to death in infected mammal hosts. Currently used acellular vaccines against anthrax consist of protective antigen (PA), one of the anthrax toxin components. However, in experimental animals such vaccines are less protective than live attenuated strains. Here we demonstrate that the addition of formaldehyde-inactivated spores (FIS) of B. anthracis to PA elicits total protection against challenge with virulent B. anthracis strains in mice and guinea pigs. The toxin-neutralizing activities of sera from mice immunized with PA alone or PA plus FIS were similar, suggesting that the protection conferred by PA plus FIS was not only a consequence of the humoral response to PA. A PA-deficient challenge strain was constructed, and its virulence was due solely to its multiplication. Immunization with FIS alone was sufficient to protect mice partially, and guinea pigs totally, against infection with this strain. This suggests that spore antigens contribute to protection. Guinea pigs and mice had very different susceptibilities to infection with the nontoxigenic strain, highlighting the importance of verifying the pertinence of animal models for evaluating anthrax vaccines.

scholarly journals Search for Correlates of Protective Immunity Conferred by Anthrax Vaccine

2001 ◽  
Vol 69 (5) ◽  
pp. 2888-2893 ◽  
Author(s):  
Shaul Reuveny ◽  
Moshe D. White ◽  
Yaakov Y. Adar ◽  
Yaron Kafri ◽  
Zeev Altboum ◽  
...  
Keyword(s):  
Antibody Titer ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Protective Antigen ◽  
Surrogate Marker ◽  
Neutralizing Antibody ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lethal Challenge ◽  
Anthrax Spores ◽  
Antibody Titers

ABSTRACT Vaccination by anthrax protective antigen (PA)-based vaccines requires multiple immunization, underlying the need to develop more efficacious vaccines or alternative vaccination regimens. In spite of the vast use of PA-based vaccines, the definition of a marker for protective immunity is still lacking. Here we describe studies designed to help define such markers. To this end we have immunized guinea pigs by different methods and monitored the immune response and the corresponding extent of protection against a lethal challenge with anthrax spores. Active immunization was performed by a single injection using one of two methods: (i) vaccination with decreasing amounts of PA and (ii) vaccination with constant amounts of PA that had been thermally inactivated for increasing periods. In both studies a direct correlation between survival and neutralizing-antibody titer was found (r 2 = 0.92 and 0.95, respectively). Most significantly, in the two protocols a similar neutralizing-antibody titer range provided 50% protection. Furthermore, in a complementary study involving passive transfer of PA hyperimmune sera to naive animals, a similar correlation between neutralizing-antibody titers and protection was found. In all three immunization studies, neutralization titers of at least 300 were sufficient to confer protection against a dose of 40 50% lethal doses (LD50) of virulent anthrax spores of the Vollum strain. Such consistency in the correlation of protective immunity with anti-PA antibody titers was not observed for antibody titers determined by an enzyme-linked immunosorbent assay. Taken together, these results clearly demonstrate that neutralizing antibodies to PA constitute a major component of the protective immunity against anthrax and suggest that this parameter could be used as a surrogate marker for protection.

scholarly journals An Adenovirus-Vectored Nasal Vaccine Confers Rapid and Sustained Protection against Anthrax in a Single-Dose Regimen

2012 ◽  
Vol 20 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Jianfeng Zhang ◽  
Edward Jex ◽  
Tsungwei Feng ◽  
Gloria S. Sivko ◽  
Leslie W. Baillie ◽  
...  
Keyword(s):  
Single Dose ◽  
Dose Regimen ◽  
Protective Antigen ◽  
Lethal Factor ◽  
Adenovirus Vector ◽  
Content Type ◽  
Inhalation Anthrax ◽  
Nasal Vaccine ◽  
Anthrax Spores ◽  
Intranasal Instillation

ABSTRACTBacillus anthracisis the causative agent of anthrax, and its spores have been developed into lethal bioweapons. To mitigate an onslaught from airborne anthrax spores that are maliciously disseminated, it is of paramount importance to develop a rapid-response anthrax vaccine that can be mass administered by nonmedical personnel during a crisis. We report here that intranasal instillation of a nonreplicating adenovirus vector encodingB. anthracisprotective antigen could confer rapid and sustained protection against inhalation anthrax in mice in a single-dose regimen in the presence of preexisting adenovirus immunity. The potency of the vaccine was greatly enhanced when codons of the antigen gene were optimized to match the tRNA pool found in human cells. In addition, an adenovirus vector encoding lethal factor can confer partial protection against inhalation anthrax and might be coadministered with a protective antigen-based vaccine.

scholarly journals Teixobactin Provides Protection against Inhalation Anthrax in the Rabbit Model

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 773 ◽  
Author(s):  
William S. Lawrence ◽  
Jennifer E. Peel ◽  
Satheesh K. Sivasubramani ◽  
Wallace B. Baze ◽  
Elbert B. Whorton ◽  
...  
Keyword(s):  
Protective Antigen ◽  
Protective Efficacy ◽  
Bacterial Load ◽  
Lethal Dose ◽  
Rabbit Model ◽  
Negative Control ◽  
Adult Rabbit ◽  
Microscopic Evaluation ◽  
Inhalation Anthrax ◽  
Anthrax Infection

The use of antibiotics is a vital means of treating infections caused by the bacteria Bacillus (B.) anthracis. Importantly, with the potential future use of multidrug-resistant strains of B. anthracis as bioweapons, new antibiotics are needed as alternative therapeutics. In this blinded study, we assessed the protective efficacy of teixobactin, a recently discovered antibiotic, against inhalation anthrax infection in the adult rabbit model. New Zealand White rabbits were infected with a lethal dose of B. anthracis Ames spores via the inhalation route, and blood samples were collected at various times to assess antigenemia, bacteremia, tissue bacterial load, and antibody production. Treatments were administered upon detection of B. anthracis protective antigen in the animals’ sera. For comparison, a fully protective dose of levofloxacin was used as a positive control. Rabbits treated with teixobactin showed 100% survival following infection, and the bacteremia was completely resolved by 24–48 h post-treatment. In addition, the bacterial/spore loads in tissues of the animals treated with teixobactin were either zero or dramatically less relative to that of the negative control animals. Moreover, microscopic evaluation of the tissues revealed decreased pathology following treatment with teixobactin. Overall, these results show that teixobactin was protective against inhalation anthrax infection in the rabbit model, and they indicate the potential of teixobactin as a therapeutic for the disease.

COVID-19: Update on Pathogenesis and Treatment Strategies

2020 ◽  
Vol 16 (1) ◽  
pp. 1-5
Author(s):  
Rakesh K. Chauhan ◽  
Pramod K. Sharma ◽  
Shikha Srivastava
Keyword(s):  
Monoclonal Antibody ◽  
Plasma Membrane ◽  
Human Monoclonal Antibody ◽  
Cardiac Injury ◽  
Treatment Strategies ◽  
Severe Pneumonia ◽  
Ground Glass Opacity ◽  
Golgi Membrane ◽  
Virus Particles ◽  
Global Pandemic

COVID-19 (Coronavirus disease) is the most contagious virus, which has been characterized as a global pandemic by WHO. The pathological cycle of COVID-19 virus can be specified as RNAaemia, severe pneumonia, along with the Ground-glass opacity (GGO), and acute cardiac injury. The S protein of Coronavirus has been reported to be involved in the entry of the virus into the host cell, which can be accomplished by direct membrane fusion between the virus and plasma membrane. In the endoplasmic reticulum or Golgi membrane, the newly formed enveloped glycoproteins are introduced. The spread of disease occurs due to contact and droplets unleashed by the vesicles holding the virus particles combined with the plasma membrane to the virus released by the host. The present manuscript describes the pathogenesis of COVID-19 and various treatment strategies that include drugs such as chloroquine and hydroxychloroquine, an anti-malarial drug, antibodies: SARS-CoV-specific human monoclonal antibody CR3022 and plasma treatment facilitate the therapeutic effect.

Effect of Egg Yolk and Phosphatides on Anthrax Infection of Rats and Guinea Pigs

1965 ◽  
Vol 118 (1) ◽  
pp. 105-108 ◽  
Author(s):  
W. D. Sawyer ◽  
R. W. Kuehne ◽  
W. S. Gochenour
Keyword(s):  
Guinea Pigs ◽  
Egg Yolk ◽  
Anthrax Infection

scholarly journals Efficacy of a Vaccine Based on Protective Antigen and Killed Spores against Experimental Inhalational Anthrax

2008 ◽  
Vol 77 (3) ◽  
pp. 1197-1207 ◽  
Author(s):  
Yves P. Gauthier ◽  
Jean-Nicolas Tournier ◽  
Jean-Charles Paucod ◽  
Jean-Philippe Corre ◽  
Michèle Mock ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Protective Immunity ◽  
Protective Antigen ◽  
Virulent Strain ◽  
Neutralizing Antibody ◽  
Cutaneous Anthrax ◽  
Anthrax Vaccines ◽  
Mucosal Secretions ◽  
Highly Virulent ◽  
Lethal Doses

ABSTRACTProtective antigen (PA)-based anthrax vaccines acting on toxins are less effective than live attenuated vaccines, suggesting that additional antigens may contribute to protective immunity. Several reports indicate that capsule or spore-associated antigens may enhance the protection afforded by PA. Addition of formaldehyde-inactivated spores (FIS) to PA (PA-FIS) elicits total protection against cutaneous anthrax. Nevertheless, vaccines that are effective against cutaneous anthrax may not be so against inhalational anthrax. The aim of this work was to optimize immunization with PA-FIS and to assess vaccine efficacy against inhalational anthrax. We assessed the immune response to recombinant anthrax PA fromBacillus anthracis(rPA)-FIS administered by various immunization protocols and the protection provided to mice and guinea pigs infected through the respiratory route with spores of a virulent strain ofB. anthracis. Combined subcutaneous plus intranasal immunization of mice yielded a mucosal immunoglobulin G response to rPA that was more than 20 times higher than that in lung mucosal secretions after subcutaneous vaccination. The titers of toxin-neutralizing antibody and antispore antibody were also significantly higher: nine and eight times higher, respectively. The optimized immunization elicited total protection of mice intranasally infected with the virulentB. anthracisstrain 17JB. Guinea pigs were fully protected, both against an intranasal challenge with 100 50% lethal doses (LD50) and against an aerosol with 75 LD50of spores of the highly virulent strain 9602. Conversely, immunization with PA alone did not elicit protection. These results demonstrate that the association of PA and spores is very much more effective than PA alone against experimental inhalational anthrax.

SEROLOGICAL AND MOLECULAR EVALUATION OF MIGRATORY TRICHINELLA SPIRALIS LARVAE IN BLOOD OF HUMANS IN KADUNA METROPOLIS, NIGERIA

2021 ◽  
Vol 4 (4) ◽  
pp. 281-289
Author(s):  
Paul Isaac Ojodale ◽  
Helen Ileigo Inabo ◽  
Elijah Ekah Ella ◽  
Oluyinka Oluseyi Okubanjo
Keyword(s):  
Trichinella Spiralis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Seroprevalence Rate ◽  
Base Pairs ◽  
Worldwide Distribution ◽  
Food Borne ◽  
Atp6 Gene ◽  
Amplicon Size ◽  
Polymerase Chain ◽  
Species Specific

Trichinellosis is an important food-borne zoonotic disease with public health implications and a worldwide distribution. In this study, Polymerase Chain Reaction (PCR) procedure using species specific ATP6 primers was used to detect the presence of migratory Trichinella spiralis larval mitochondrial ATP6 synthase F0 subunit (ATP6) gene, after detection of antibodies to Trichinella excretory-secretory (E/S) antigen using Enzyme-linked Immunosorbent Assay (ELISA), in blood of humans in Kaduna metropolis, Nigeria. The sera of 210 participants were tested for antibodies to Trichinella E/S antigen. Overall seroprevalence rate of 39% (82/210) was recorded using ELISA. Out of the 9 ELISA samples selected randomly, PCR detected migratory Trichinella spiralis larval ATP6 gene in 4 (44.4%) at the amplicon size of 250 base pairs using the whole blood of the participants.  The 9 samples comprised 7 seropositive and 2 seronegative. The bands at lanes 1, 2, 3 and 4 were positive for ATP6 while lanes 5,6,7,8 and 9 were negative for ATP6.  Lanes 4 and 5 were ELISA negative for anti-Trichinella antibodies. One in 5 of the 128 ELISA negative samples was positive for ATP6 representing a 25.6% prevalence rate by extrapolation.  PCR using ATP6 gene as a genetic marker is valuable for the detection of T. spiralis migratory larvae in blood samples of humans and consequently the early diagnosis of trichinellosis in humans.

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