Passive vaccination with a human monoclonal antibody: Generation of antibodies and studies for efficacy in Bacillus anthracis infections

Esche, Ulrich vor dem; Huber, Maria; Zgaga-Griesz, A.; Grunow, Roland; Beyer, Wolfgang; Hahn, Ulrike; Bessler, Wolfgang G.

doi:10.1016/j.imbio.2010.12.001

Cited by 15 publications

(6 citation statements)

References 25 publications

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“…Artificially induced fusion can be used to investigate and treat different diseases, like diabetes123, regenerate axons of the central nerve system4, and produce cells with desired properties, such as in cell vaccines for cancer immunotherapy567. However, the first and most known application of cell fusion is production of monoclonal antibodies in hybridoma technology, where hybrid cell lines (hybridomas) are formed by fusing specific antibody-producing B lymphocytes with a myeloma (B lymphocyte cancer) cell line89. Myeloma cells were selected for their ability to grow in culture, since B lymphocytes do not survive outside their natural environment.…”

mentioning

confidence: 99%

Cell electrofusion using nanosecond electric pulses

Rems

Ušaj

Kandušer

et al. 2013

Sci Rep

115

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Electrofusion is an efficient method for fusing cells using short-duration high-voltage electric pulses. However, electrofusion yields are very low when fusion partner cells differ considerably in their size, since the extent of electroporation (consequently membrane fusogenic state) with conventionally used microsecond pulses depends proportionally on the cell radius. We here propose a new and innovative approach to fuse cells with shorter, nanosecond (ns) pulses. Using numerical calculations we demonstrate that ns pulses can induce selective electroporation of the contact areas between cells (i.e. the target areas), regardless of the cell size. We then confirm experimentally on B16-F1 and CHO cell lines that electrofusion of cells with either equal or different size by using ns pulses is indeed feasible. Based on our results we expect that ns pulses can improve fusion yields in electrofusion of cells with different size, such as myeloma cells and B lymphocytes in hybridoma technology.

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mentioning

confidence: 99%

Cell electrofusion using nanosecond electric pulses

Rems

Ušaj

Kandušer

et al. 2013

Sci Rep

115

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“…Though several clones producing PA specific Ig were obtained; only one clone (hLF1-SAN) produced a monoclonal antibody (hLF1) directed against LF. hLF1 was able to neutralize anthrax toxin activity in an in vitro neutralization assay, and preliminary in vivo studies in mice also indicated a trend towards protection [114]. The epitope of the antibody binding to LF was mapped and the results suggest the binding of the monoclonal antibody to the peptide regions 121-150 or 451-470 of LF.…”

Section: Monoclonal Antibodies For Passive Immunizationmentioning

confidence: 93%

Recent progress in the development of anthrax vaccines

Kaur¹,

Bhatnagar

2011

BIOT

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Bacillus anthracis is the etiological agent of anthrax. Although anthrax is primarily an epizootic disease; humans are at risk for contracting anthrax. The potential use of B. anthracis spores as biowarfare agent has led to immense attention. Prolonged vaccination schedule of current anthrax vaccine and variable protection conferred; often leading to failure of therapy. This highlights the need for alternative anthrax countermeasures. A number of approaches are being investigated to substitute or supplement the existing anthrax vaccines. These relied on expression of Protective antigen (PA), the key protective immunogen; in bacterial or plant systems; or utilization of attenuated strains of B. anthracis for immunization. Few studies have established potential of domain IV of PA for immunization. Other targets including the spore, capsule, S-layer and anthrax toxin components have been investigated for imparting protective immunity. It has been shown that co-immunization of PA with domain I of lethal factor that binds PA resulted in higher antibody responses. Of the epitope based vaccines, the loop neutralizing determinant, in particular; elicited robust neutralizing antibody response and conferred 97% protection upon challenge. DNA vaccination resulted in varying degree of protection and seems a promising approach. Additionally, the applicability of monoclonal and therapeutic antibodies in the treatment of anthrax has also been demonstrated. The recent progress in the direction of anthrax prophylaxis has been evaluated in this review.

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“…A high affinity scFv (2LF) generated against LF in macaques and described as humanlike inhibited LF binding to PA 63 and was protective in the macrophage lysis assay and in LT-challenged Fisher rats [93]. One group combined antibody-producing lymphocytes from individuals vaccinated with the UK anthrax vaccine with a human–mouse heteromyeloma cell line (CB-F7) and developed mAb to LF (hLF1-SAN) [94]. This mAb bound to peptide regions 121 – 150 and 451 – 470 of LF and was protective in an LT neutralization assay and in LT-challenged mice.…”

Section: Toxin-directed Therapies For the Management Of B Anthracmentioning

confidence: 99%

An overview of investigational toxin-directed therapies for the adjunctive management ofBacillus anthracisinfection and sepsis

Ohanjanian

Remy

et al. 2015

Expert Opinion on Investigational Drugs

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Introduction Sepsis with Bacillus anthracis infection has a very high mortality rate despite appropriate antibiotic and supportive therapies. Over the past 15 years, recent outbreaks in the US and in Europe, coupled with anthrax's bioterrorism weapon potential, have stimulated efforts to develop adjunctive therapies to improve clinical outcomes. Since lethal toxin and edema toxin (LT and ET) make central contributions to the pathogenesis of B. anthracis, these have been major targets in this effort. Areas covered Here, the authors review different investigative biopharmaceuticals that have been recently identified for their therapeutic potential as inhibitors of LT or ET. Among these inhibitors are two antibody preparations that have been included in the Strategic National Stockpile (SNS) and several more that have reached Phase I testing. Presently, however, many of these candidate agents have only been studied in vitro and very few tested in bacteria-challenged models. Expert opinion Although a large number of drugs have been identified as potential therapeutic inhibitors of LT and ET, in most cases their testing has been limited. The use of the two SNS antibody therapies during a large-scale exposure to B. anthracis will be difficult. Further testing and development of agents with oral bioavailability and relatively long shelf lives should be a focus for future research.

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Passive vaccination with a human monoclonal antibody: Generation of antibodies and studies for efficacy in Bacillus anthracis infections

Cited by 15 publications

References 25 publications

Cell electrofusion using nanosecond electric pulses

Cell electrofusion using nanosecond electric pulses

Recent progress in the development of anthrax vaccines

An overview of investigational toxin-directed therapies for the adjunctive management ofBacillus anthracisinfection and sepsis

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