A recombinant chimeric protein containing B chains of ricin and abrin is an effective vaccine candidate

Hum Vaccin Immunother. 2014;10(4):938-44. doi: 10.4161/hv.27870. Epub 2014 Feb 7.

Abstract

Both ricin toxin (RT) and abrin toxin (AT) are 2 important toxin agents as potantial bioweapons. A dual subunit vaccine against RT and AT exposure is a promising option for developing prophylactic vaccination. In this study, we constructed a dual vaccine with RT B chain and AT B chain named RTB-ATB. The RTB-ATB chimeric protein was expressed in Escherichia coli (E. coli), and the purified protein was used to evaluate the immune response by a 2 × 2 × 2 × 2 factorial design. The main effects included dose of RTB-ATB, route of immunization injection, immunization time interval, and dose of native toxins challenge. For 2 × LD(50) challenge of RT or AT, 100% of the RTB-ATB immunized mice survived and regained or exceeded their initial weights within 10 days. For 4 × LD(50) challenge, different routes of immunization injection caused significant difference (P < 0.05), intraperitoneal (i.p.) administration of immunogen protected mice better than the subcutaneous (s.c.) administration. In conclusion, when administered i.p. to mice with 25 μg per mouse and immunization time interval Π in the absence of adjuvant, the chimeric protein elicited a stronger immune response and protected the animals from a dose of native toxins which was 4 times higher than their LD(50) in unvaccinated mice. Besides, the RTB-ATB chimeric protein could induce specific neutralizing antibodies against these 2 toxins. We anticipate that this study will open new possibilities in the preparation of RTB-ATB dual subunit vaccine against the exposure to deadly RT and AT.

Keywords: B chain; abrin; bioterrorism; chimeric protein; immunogen; ricin; vaccine candidate.

MeSH terms

  • Abrin / genetics
  • Abrin / immunology*
  • Animals
  • Disease Models, Animal
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Female
  • Gene Expression
  • Immunization / methods
  • Mice, Inbred BALB C
  • Poisoning / immunology
  • Poisoning / prevention & control*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / isolation & purification
  • Ricin / genetics
  • Ricin / immunology*
  • Survival Analysis
  • Vaccines, Subunit / administration & dosage*
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Recombinant Fusion Proteins
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Abrin
  • Ricin