ArticlePloS one2013
In vivo neutralization of α-cobratoxin with high-affinity llama single-domain antibodies (VHHs) and a VHH-Fc antibody.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 115 citations in OpenAlex.
- Multiobjective VScience advances · 2026Article
- Engineering Antivenom: Research Progress and Future Directions in Snakebite Envenoming Therapy.Annals of the New York Academy of Sciences · 2026Review
- Targeting Key Enzymatic Snake Venom Proteins Using Repurposed Small Molecule Inhibitors: Emerging Adjuncts to Antivenom Therapy.International journal of molecular sciences · 2026Review
- Bispecific single-domain antibody (VHH) fused with human IgG1 Fc with dual specificity effectively neutralize Naja Kaouthia venom.PLoS neglected tropical diseases · 2026Article
- Large animal models for the assessment of snakebite envenoming therapies.npj drug discovery · 2026Review
- Comment on: What is new in the treatment of snakebite envenoming? Opportunities and challenges.Transactions of the Royal Society of Tropical Medicine and Hygiene · 2025Article
- Protein-based tools for the detection and characterisation of Oropouche virus infection.EMBO molecular medicine · 2025Article
- Neutralization of the Pandemic Influenza A/H1N1 Virus withAntibodies (Basel, Switzerland) · 2025Article
- Target product profiles for pan-Africa recombinant antivenoms against neurotoxic or hemotoxic and cytotoxic snakebite envenoming.PLoS neglected tropical diseases · 2025Article
- Neutralizing Nanobodies against Venoms fromToxins · 2024Article
- Article
- Phage display-derived alpaca nanobodies as potential therapeutics forApplied and environmental microbiology · 2024Article
- Characterization of plant produced VBiotechnology reports (Amsterdam, Netherlands) · 2024Article
- Development of a new affinity maturation protocol for the construction of an internalizing anti-nucleolin antibody library.Scientific reports · 2024Article
- Recombinant snake antivenoms get closer to the clinic.Trends in immunology · 2024Article
- Review
- Review
- Profiling Germinal Center-like B Cell Responses to Conjugate Vaccines Using Synthetic Immune Organoids.ACS central science · 2023Article
- NANOBODIES®: A Review of Diagnostic and Therapeutic ApplicationsInternational journal of molecular sciences · 2023Review
- Towards better antivenoms: navigating the road to new types of snakebite envenoming therapies.The journal of venomous animals and toxins including tropical diseases · 2023Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small recombinant antibody fragments (e.g. scFvs and VHHs), which are highly tissue permeable, are being investigated for antivenom production as conventional antivenoms consisting of IgG or F(ab')2 antibody fragments do not effectively neutralize venom toxins located in deep tissues. However, antivenoms composed entirely of small antibody fragments may have poor therapeutic efficacy due to their short serum half-lives. To increase serum persistence and maintain tissue penetration, we prepared low and high molecular mass antivenom antibodies. Four llama VHHs were isolated from an immune VHH-displayed phage library and were shown to have high affinity, in the low nM range, for α-cobratoxin (α-Cbtx), the most lethal component of Naja kaouthia venom. Subsequently, our highest affinity VHH (C2) was fused to a human Fc fragment to create a VHH2-Fc antibody that would offer prolonged serum persistence. After in planta (Nicotiana benthamiana) expression and purification, we show that our VHH2-Fc antibody retained high affinity binding to α-Cbtx. Mouse α-Cbtx challenge studies showed that our highest affinity VHHs (C2 and C20) and the VHH2-Fc antibody effectively neutralized lethality induced by α-Cbtx at an antibody:toxin molar ratio as low as ca. 0.75×:1. Further research towards the development of an antivenom therapeutic involving these anti-α-Cbtx VHHs and VHH2-Fc antibody molecules should involve testing them as a combination, to determine whether they maintain tissue penetration capability and low immunogenicity, and whether they exhibit improved serum persistence and therapeutic efficacy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.