ArticleClinical and vaccine immunology : CVI2010
Efficacy of a potential trivalent vaccine based on Hc fragments of botulinum toxins A, B, and E produced in a cell-free expression system.
Article in Clinical and vaccine immunology : CVI, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- Cancer Antibody Engineering: Comparison of Mammalian, Yeast, Bacterial, Plants, Cell-free and Hybridoma Expression Systems.Current pharmaceutical biotechnology · 2025Review
- Circumventing the Impossible: Cell-Free Synthesis of Protein Toxins for Medical and Diagnostic Applications.International journal of molecular sciences · 2024Review
- Synthesis of biologically active Shiga toxins in cell-free systems.Scientific reports · 2024Article
- Novel platform for engineering stable and effective vaccines against botulinum neurotoxins A, B and E.Frontiers in immunology · 2024Article
- Development and evaluation of a tetravalent botulinum vaccine.Human vaccines & immunotherapeutics · 2022Article
- Immunologic and Protective Properties of Subunit- vs. Whole Toxoid-Derived Anti-Botulinum Equine Antitoxin.Vaccines · 2022Article
- High Cell Density Cultivation Process for the Expression of Botulinum Neurotoxin a Receptor Binding Domain.Toxins · 2022Article
- Cell-Free Systems Enable the Production of ABToxins · 2022Article
- Efficient production of immunologically active Shigella invasion plasmid antigens IpaB and IpaH using a cell-free expression system.Applied microbiology and biotechnology · 2022Article
- Immunoinformatic analysis of the whole proteome for vaccine design: An application toFrontiers in immunology · 2022Article
- Centaur antibodies: Engineered chimeric equine-human recombinant antibodies.Frontiers in immunology · 2022Article
- Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development.Toxins · 2020Review
- Cell-Free Protein Synthesis: A Promising Option for Future Drug Development.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2020Review
- Antibodies and Vaccines against Botulinum Toxins: Available Measures and Novel Approaches.Toxins · 2019Review
- Review
- Synthetic Biology Goes Cell-Free.BMC biology · 2019Review
- Intradermal immunization with botulinum neurotoxin serotype E DNA vaccine induces humoral and cellular immunity and protects against lethal toxin challenge.Human vaccines & immunotherapeutics · 2019Article
- Exploring the Potential of Cell-Free Protein Synthesis for Extending the Abilities of Biological Systems.Frontiers in bioengineering and biotechnology · 2019Review
- Article
- Development of a multiplex Endopep-MS assay for simultaneous detection of botulinum toxins A, B and E.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Botulinum toxins produced by the anaerobic bacterium Clostridium botulinum are the most potent biological toxins in nature. Traditionally, people at risk are immunized with a formaldehyde-inactivated toxin complex. Second generation vaccines are based on the recombinant carboxy-terminal heavy-chain (Hc) fragment of the neurotoxin. However, the materialization of this approach is challenging, mainly due to the high AT content of clostridial genes. Herein, we present an alternative strategy in which the native genes encoding Hc proteins of botulinum toxins A, B, and E were used to express the recombinant Hc fragments in a cell-free expression system. We used the unique property of this open system to introduce different combinations of chaperone systems, protein disulfide isomerase (PDI), and reducing/oxidizing environments directly to the expression reaction. Optimized expression conditions led to increased production of soluble Hc protein, which was successfully scaled up using a continuous exchange (CE) cell-free system. Hc proteins were produced at a concentration of more than 1 mg/ml and purified by one-step Ni(+) affinity chromatography. Mice immunized with three injections containing 5 microg of any of the in vitro-expressed, alum-absorbed, Hc vaccines generated a serum enzyme-linked immunosorbent assay (ELISA) titer of 10(5) against the native toxin complex, which enabled protection against a high-dose toxin challenge (10(3) to 10(6) mouse 50% lethal dose [MsLD(50)]). Finally, immunization with a trivalent HcA, HcB, and HcE vaccine protected mice against the corresponding trivalent 10(5) MsLD(50) toxin challenge. Our results together with the latest developments in scalability of the in vitro protein expression systems offer alternative routes for the preparation of botulinum vaccine.
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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.