Structure of RiVax: A recombinant ricin vaccine

Patricia M. Legler, Robert N. Brey, Joan E. Smallshaw, Ellen S. Vitetta, Charles B. Millard

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)826-830
Number of pages5
JournalActa Crystallographica Section D: Biological Crystallography
Volume67
Issue number9
DOIs
StatePublished - Sep 2011

Fingerprint

Ricin
Synthetic Vaccines
Vaccines
Ricinus
B-Lymphocyte Epitopes
Protein Engineering
Amino Acid Substitution
Catalysis
Recombinant Proteins
Poisoning
Epitopes
RiVax

Keywords

  • B-cell epitopes
  • immunogens
  • protein engineering
  • ribosome-inactivating proteins
  • ricin
  • RiVax

ASJC Scopus subject areas

  • Structural Biology

Cite this

Structure of RiVax : A recombinant ricin vaccine. / Legler, Patricia M.; Brey, Robert N.; Smallshaw, Joan E.; Vitetta, Ellen S.; Millard, Charles B.

In: Acta Crystallographica Section D: Biological Crystallography, Vol. 67, No. 9, 09.2011, p. 826-830.

Research output: Contribution to journalArticle

Legler, Patricia M. ; Brey, Robert N. ; Smallshaw, Joan E. ; Vitetta, Ellen S. ; Millard, Charles B. / Structure of RiVax : A recombinant ricin vaccine. In: Acta Crystallographica Section D: Biological Crystallography. 2011 ; Vol. 67, No. 9. pp. 826-830.
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