Standardized, mathematical model-based and validated in vitro analysis of anthrax lethal toxin neutralization

Li, Han; Soroka, Stephen; Taylor, Thomas H.; Stamey, Karen; Stinson, Kelly Wallace; Freeman, Alison; Abramson, Darbi R.; Desai, Rita; Cronin, Li; Oxford, J. Wade; Caba, Joseph; Pleatman, Cynthia; Pathak, Sonal; Schmidt, Daniel S.; Semenova, Vera; Martin, Sandra; Wilkins, Patricia P.; Quinn, Conrad P.

doi:10.1016/j.jim.2008.01.007

Cited by 65 publications

(73 citation statements)

References 47 publications

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“…TNA assays were done according to the method of Li et al (20), using human reference standard AVR801 (44). Reportable values were the reciprocal serum sample dilutions effecting 50% neutralization of anthrax lethal toxin (ED 50 ).…”

mentioning

confidence: 99%

A Three-Dose Intramuscular Injection Schedule of Anthrax Vaccine Adsorbed Generates Sustained Humoral and Cellular Immune Responses to Protective Antigen and Provides Long-Term Protection against Inhalation Anthrax in Rhesus Macaques

Quinn¹,

Sabourin²,

Niemuth³

et al. 2012

Clin. Vaccine Immunol.

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05). PA-specific gamma interferon (IFN-␥) and interleukin-4 (IL-4) CD4؉ cell frequencies and T cell stimulation indices were sustained through 50.5 months (the last time point measured). PA-specific memory B cell frequencies were highly variable but, in general, were detectable in peripheral blood mononuclear cells (PBMC) by 2 months, were significantly above control levels by 7 months, and remained detectable in the HuAVA and 1:5 and 1:20 AVA groups through 42 months (the last time point measured). HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming, with sustained production of high-avidity PA-specific functional antibody, long-term immune cell competence, and immunological memory (30 months for 1:20 AVA and 52 months for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high-magnitude anamnestic anti-PA IgG and TNA responses.

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confidence: 99%

A Three-Dose Intramuscular Injection Schedule of Anthrax Vaccine Adsorbed Generates Sustained Humoral and Cellular Immune Responses to Protective Antigen and Provides Long-Term Protection against Inhalation Anthrax in Rhesus Macaques

Quinn¹,

Sabourin²,

Niemuth³

et al. 2012

Clin. Vaccine Immunol.

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“…Figure 1 shows the neutralization curves in the two assays for two neutralizing MAbs, AVR1046 and F20G75. AVR1046 is a murine IgG1 (18). We mapped the epitope for this MAb to domain 4 (amino acids 596 to 735) of PA, the receptor binding domain, using purified PA domains and immunoblot analysis as described in Materials and Methods (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…Anti-PA-producing hybridomas were subcloned three times for isolation of antibodyproducing cells. Generated MAbs were further screened for their ability to neutralize LT activity in a J774A.1 cell-based assay (18). F20G75 and 2F9 were prepared and characterized as described by Gubbins et TNA assays.…”

Section: Methodsmentioning

confidence: 99%

Analysis of Defined Combinations of Monoclonal Antibodies in Anthrax Toxin Neutralization Assays and Their Synergistic Action

Ngundi

Meade

Little

et al. 2012

Clin. Vaccine Immunol.

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ABSTRACTAntibodies against the protective antigen (PA) component of anthrax toxin play an important role in protection against disease caused byBacillus anthracis. In this study, we examined defined combinations of PA-specific monoclonal antibodies for their ability to neutralize anthrax toxin in cell culture assays. We observed additive, synergistic, and antagonistic effects of the antibodies depending on the specific antibody combination examined and the specific assay used. Synergistic toxin-neutralizing antibody interactions were examined in more detail. We found that one mechanism that can lead to antibody synergy is the bridging of PA monomers by one antibody, with resultant bivalent binding of the second antibody. These results may aid in optimal design of new vaccines and antibody therapies against anthrax.

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“…An ELISA was used to determine the titers of anti-PA IgG antibodies. 4 The J774A.1 cellbased toxin neutralization assay was performed essentially as described by Li et al 26 and a detailed description is given in the Supplemental Materials section. our in vivo bioluminescence imaging data are concordant with what we observed in the vaccinated rabbits thus underscoring the utility of this A/J mouse model despite its inherent limitations to explore certain aspects of host-pathogen interactions in a less restrictive laboratory environment in a cost effective manner.…”

Section: Methodsmentioning

confidence: 99%

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

Merkel

Perera

Lee

et al. 2013

Human Vaccines & Immunotherapeutics

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Standardized, mathematical model-based and validated in vitro analysis of anthrax lethal toxin neutralization

Cited by 65 publications

References 47 publications

A Three-Dose Intramuscular Injection Schedule of Anthrax Vaccine Adsorbed Generates Sustained Humoral and Cellular Immune Responses to Protective Antigen and Provides Long-Term Protection against Inhalation Anthrax in Rhesus Macaques

A Three-Dose Intramuscular Injection Schedule of Anthrax Vaccine Adsorbed Generates Sustained Humoral and Cellular Immune Responses to Protective Antigen and Provides Long-Term Protection against Inhalation Anthrax in Rhesus Macaques

Analysis of Defined Combinations of Monoclonal Antibodies in Anthrax Toxin Neutralization Assays and Their Synergistic Action

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

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