Structure of RiVax: a recombinant ricin vaccine
- Naval Research Laboratories, 4555 Overlook Avenue, Washington, DC 20375 (United States)
- Soligenix Inc., 29 Emmons Drive, Suite C-10, Princeton, NJ 08540 (United States)
- UT Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, TX 75390-8576 (United States)
The X-ray crystal structure (at 2.1 Å resolution) of an immunogen under development as part of a ricin vaccine for humans is presented and structure-based analysis of the results was conducted with respect to related proteins and the known determinants for inducing or suppressing the protective immune response. RiVax is a recombinant protein that is currently under clinical development as part of a human vaccine to protect against ricin poisoning. RiVax includes ricin A-chain (RTA) residues 1–267 with two intentional amino-acid substitutions, V76M and Y80A, aimed at reducing toxicity. Here, the crystal structure of RiVax was solved to 2.1 Å resolution and it was shown that it is superposable with that of the ricin toxin A-chain from Ricinus communis with a root-mean-square deviation of 0.6 Å over 258 C{sup α} atoms. The RiVax structure is also compared with the recently determined structure of another potential ricin-vaccine immunogen, RTA 1–33/44–198 R48C/T77C. Finally, the locations and solvent-exposure of two toxin-neutralizing B-cell epitopes were examined and it was found that these epitopes are within or near regions predicted to be involved in catalysis. The results demonstrate the composition of the RiVax clinical material and will guide ongoing protein-engineering strategies to develop improved immunogens.
- OSTI ID:
- 22347902
- Journal Information:
- Acta Crystallographica. Section D: Biological Crystallography, Vol. 67, Issue Pt 9; Other Information: PMCID: PMC3169317; PMID: 21904036; PUBLISHER-ID: gx5187; OAI: oai:pubmedcentral.nih.gov:3169317; Copyright (c) Legler et al. 2011; This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0907-4449
- Country of Publication:
- Denmark
- Language:
- English
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