Recent advances in the development of vaccines against ricin

Robert N. Brey, Nicholas J. Mantis, Seth H. Pincus, Ellen S. Vitetta, Leonard A. Smith, Chad J. Roy

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Several promising subunit vaccines against ricin toxin (RT) have been developed during the last decade and are now being tested for safety and immunogenicity in humans and for efficacy in nonhuman primates. The incentive to develop a preventive vaccine as a countermeasure against RT use as a bioweapon is based on the high toxicity of RT after aerosol exposure, its environmental stability, abundance, and ease of purification. RT is the second most lethal biological toxin and is considered a “universal toxin” because it can kill all eukaryotic cells through binding to ubiquitous cell surface galactosyl residues. RT has two subunits conjoined by a single disulfide linkage: RTB, which binds galactosyl residues and RTA which enzymatically inactivates ribosomes intracellularly by cleavage ribosomal RNA. Attenuation of toxicity by elimination of the active site or introduction of other structural mutations of RTA has generated two similar clinical subunit vaccine candidates which induce antibodies in both humans and nonhuman primates. In rhesus macaques, inhaled RT causes rapid lung necrosis and fibrosis followed by death. After parenteral vaccination with RTA vaccine, macaques can be protected against aerosol RT exposure, suggesting that circulating antibodies can protect lung mucosa. Vaccination induces RT-neutralizing antibodies, the most likely correlate of protection. Macaques responded to conformational determinants in an RTA vaccine formulation, indicating preservation of RTA structure during initial manufacture. Comparative mapping studies have also demonstrated that macaques and humans recognize the same epitopes, significant in the study of macaques as a model during development of vaccines which cannot be tested for efficacy in humans.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalHuman Vaccines and Immunotherapeutics
DOIs
StateAccepted/In press - Mar 16 2016

Fingerprint

Ricin
Vaccines
Macaca
Subunit Vaccines
Aerosols
Primates
Biological Toxins
Vaccination
Lung
Ribosomal RNA
Antibodies
Environmental Exposure
Eukaryotic Cells
Neutralizing Antibodies
Macaca mulatta
Ribosomes
Disulfides
Motivation
Epitopes
Catalytic Domain

Keywords

  • aerosol
  • antibody
  • epitope
  • immunization
  • non-human primate
  • ricin toxin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Recent advances in the development of vaccines against ricin. / Brey, Robert N.; Mantis, Nicholas J.; Pincus, Seth H.; Vitetta, Ellen S.; Smith, Leonard A.; Roy, Chad J.

In: Human Vaccines and Immunotherapeutics, 16.03.2016, p. 1-6.

Research output: Contribution to journalArticle

Brey, Robert N. ; Mantis, Nicholas J. ; Pincus, Seth H. ; Vitetta, Ellen S. ; Smith, Leonard A. ; Roy, Chad J. / Recent advances in the development of vaccines against ricin. In: Human Vaccines and Immunotherapeutics. 2016 ; pp. 1-6.
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