ArticleThe Journal of biological chemistry2016
High Throughput Combinatorial Formatting of PcrV Nanobodies for Efficient Potency Improvement.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment.Frontiers in immunology · 2021Pooled it
- Article
- Nanobodies in the fight against infectious diseases: repurposing nature's tiny weapons.World journal of microbiology & biotechnology · 2024Review
- Nanobodies as potential tools for microbiological testing of live biotherapeutic products.AMB Express · 2024Article
- Nanobodies: Robust miniprotein binders in biomedicine.Advanced drug delivery reviews · 2023Review
- Recent advances in therapeutic targets identification and development of treatment strategies towards Pseudomonas aeruginosa infections.BMC microbiology · 2023Review
- Vaccination of mice with hybrid protein containing Exotoxin S and PcrV with adjuvants alum and MPL protects Pseudomonas aeruginosa infections.Scientific reports · 2022Article
- Research progress and applications of nanobody in human infectious diseases.Frontiers in pharmacology · 2022Review
- Pseudomonas aeruginosa Antivirulence Strategies: Targeting the Type III Secretion System.Advances in experimental medicine and biology · 2022Article
- Targeting bacterial pathogenesis by inhibiting virulence-associated Type III and Type IV secretion systems.Frontiers in cellular and infection microbiology · 2022Review
- Fluorothiazinon, a small-molecular inhibitor of T3SS, suppresses salmonella oral infection in mice.The Journal of antibiotics · 2021Article
- Recombinant expression of nanobodies and nanobody-derived immunoreagents.Protein expression and purification · 2020Review
- Antibodies Inhibiting the Type III Secretion System of Gram-Negative Pathogenic Bacteria.Antibodies (Basel, Switzerland) · 2020Review
- Rational Design of a Chimeric Derivative of PcrV as a Subunit Vaccine AgainstFrontiers in immunology · 2019Article
- The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth.Oncogene · 2018Article
- Small Molecule Inhibitor of Type Three Secretion System Belonging to a Class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones Improves Survival and Decreases Bacterial Loads in an AirwayBioMed research international · 2018Article
- Single-domain antibodies pinpoint potential targets withinThe Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Improving potencies through concomitant blockage of multiple epitopes and avid binding by fusing multiple (different) monovalent Nanobody building blocks via linker sequences into one multivalent polypeptide chain is an elegant alternative to affinity maturation. We explored a large and random formatting library of bivalent (combinations of two identical) and biparatopic (combinations of two different) Nanobodies for functional blockade of Pseudomonas aeruginosa PcrV. PcrV is an essential part of the P. aeruginosa type III secretion system (T3SS), and its oligomeric nature allows for multiple complex binding and blocking options. The library screening yielded a large number of promising biparatopic lead candidates, revealing significant (and non-trivial) preferences in terms of Nanobody building block and epitope bin combinations and orientations. Excellent potencies were confirmed upon further characterization in two different P. aeruginosa T3SS-mediated cytotoxicity assays. Three biparatopic Nanobodies were evaluated in a lethal mouse P. aeruginosa challenge pneumonia model, conferring 100% survival upon prophylactic administration and reducing lung P. aeruginosa burden by up to 2 logs. At very low doses, they protected the mice from P. aeruginosa infection-related changes in lung histology, myeloperoxidase production, and lung weight. Importantly, the most potent Nanobody still conferred protection after therapeutic administration up to 24 h post-infection. The concept of screening such formatting libraries for potency improvement is applicable to other targets and biological therapeutic platforms.
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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.