ArticleThe Journal of biological chemistry2015
A heterodimer of a VHH (variable domains of camelid heavy chain-only) antibody that inhibits anthrax toxin cell binding linked to a VHH antibody that blocks oligomer formation is highly protective in an anthrax spore challenge model.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 39 citations in OpenAlex.
- Ultrapotent neutralization of Bacillus anthracis toxin by a human antibody via blockade of PA oligomerization.PLoS pathogens · 2026Article
- Article
- Bispecific antibody engineered from two non-protective antibodies confers full protection against anthrax toxin through inhibition of PA83 cleavage.Microbiology spectrum · 2025Article
- Small but Mighty: Nanobodies in the Fight Against Infectious Diseases.Biomolecules · 2025Review
- Single domain antibodies from camelids in the treatment of microbial infections.Frontiers in immunology · 2024Review
- Article
- Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Structure-guided design of a potentFrontiers in microbiology · 2023Article
- Single domain antibodies against enteric pathogen virulence factors are active as curli fiber fusions on probiotic E. coli Nissle 1917.PLoS pathogens · 2022Article
- Intramuscular delivery of formulated RNA encoding six linked nanobodies is highly protective for exposures to three Botulinum neurotoxin serotypes.Scientific reports · 2022Article
- Single Domain Antibody application in bacterial infection diagnosis and neutralization.Frontiers in immunology · 2022Review
- Identification and characterization of a new 34 kDa MORN motif-containing sporozoite surface-exposed protein, Cp-P34, unique to Cryptosporidium.International journal for parasitology · 2021Article
- A novel single-domain antibody multimer that potently neutralizes tetanus neurotoxin.Vaccine: X · 2021Article
- Self-Assembled Nanobodies as Selectively Targeted, Nanostructured, and Multivalent Materials.ACS applied materials & interfaces · 2021Article
- Developing Recombinant Antibodies by Phage Display Against Infectious Diseases and Toxins for Diagnostics and Therapy.Frontiers in cellular and infection microbiology · 2021Review
- Urine-Based Antigen (Protein) Detection Test for the Diagnosis of Visceral Leishmaniasis.Microorganisms · 2020Review
- Camelid VHH Antibodies that Neutralize Botulinum Neurotoxin Serotype E Intoxication or Protease Function.Toxins · 2020Article
- Genomic analysis of the domestication and post-Spanish conquest evolution of the llama and alpaca.Genome biology · 2020Article
- Structural Insights into Rational Design of Single-Domain Antibody-Based Antitoxins against Botulinum Neurotoxins.Cell reports · 2020Article
- Rapid Discovery and Characterization of Synthetic Neutralizing Antibodies against Anthrax Edema Toxin.Biochemistry · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Anthrax disease is caused by a toxin consisting of protective antigen (PA), lethal factor, and edema factor. Antibodies against PA have been shown to be protective against the disease. Variable domains of camelid heavy chain-only antibodies (VHHs) with affinity for PA were obtained from immunized alpacas and screened for anthrax neutralizing activity in macrophage toxicity assays. Two classes of neutralizing VHHs were identified recognizing distinct, non-overlapping epitopes. One class recognizes domain 4 of PA at a well characterized neutralizing site through which PA binds to its cellular receptor. A second neutralizing VHH (JKH-C7) recognizes a novel epitope. This antibody inhibits conversion of the PA oligomer from "pre-pore" to its SDS and heat-resistant "pore" conformation while not preventing cleavage of full-length 83-kDa PA (PA83) by cell surface proteases to its oligomer-competent 63-kDa form (PA63). The antibody prevents endocytosis of the cell surface-generated PA63 subunit but not preformed PA63 oligomers formed in solution. JKH-C7 and the receptor-blocking VHH class (JIK-B8) were expressed as a heterodimeric VHH-based neutralizing agent (VNA2-PA). This VNA displayed improved neutralizing potency in cell assays and protected mice from anthrax toxin challenge with much better efficacy than the separate component VHHs. The VNA protected virtually all mice when separately administered at a 1:1 ratio to toxin and protected mice against Bacillus anthracis spore infection. Thus, our studies show the potential of VNAs as anthrax therapeutics. Due to their simple and stable nature, VNAs should be amenable to genetic delivery or administration via respiratory routes.
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