LT-IIb(T13I), a non-toxic type II heat-labile enterotoxin, augments the capacity of a ricin toxin subunit vaccine to evoke neutralizing antibodies and protective immunity

PLoS One. 2013 Aug 2;8(8):e69678. doi: 10.1371/journal.pone.0069678. Print 2013.

Abstract

Currently, there is a shortage of adjuvants that can be employed with protein subunit vaccines to enhance protection against biological threats. LT-IIb(T13I) is an engineered nontoxic derivative of LT-IIb, a member of the type II subfamily of heat labile enterotoxins expressed by Escherichia coli, that possesses potent mucosal adjuvant properties. In this study we evaluated the capacity of LT-IIb(T13I) to augment the potency of RiVax, a recombinant ricin toxin A subunit vaccine, when co-administered to mice via the intradermal (i.d.) and intranasal (i.n.) routes. We report that co-administration of RiVax with LT-IIb(T13I) by the i.d. route enhanced the levels of RiVax-specific serum IgG antibodies (Ab) and elevated the ratio of ricin-neutralizing to non-neutralizing Ab, as compared to RiVax alone. Protection against a lethal ricin challenge was also augmented by LT-IIb(T13I). While local inflammatory responses elicited by LT-IIb(T13I) were comparable to those elicited by aluminum salts (Imject®), LT-IIb(T13I) was more effective than aluminum salts at augmenting production of RiVax-specific serum IgG. Finally, i.n. administration of RiVax with LT-IIb(T13I) also increased levels of RiVax-specific serum and mucosal Ab and enhanced protection against ricin challenge. Collectively, these data highlight the potential of LT-IIb(T13I) as an effective next-generation i.d., or possibly i.n. adjuvant for enhancing the immunogenicity of subunit vaccines for biodefense.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / therapeutic use
  • Bacterial Toxins / administration & dosage*
  • Bacterial Toxins / immunology
  • Bacterial Toxins / metabolism
  • Drug Synergism
  • Enterotoxins / administration & dosage*
  • Enterotoxins / immunology
  • Enterotoxins / metabolism
  • Escherichia coli Proteins / administration & dosage*
  • Escherichia coli Proteins / immunology
  • Escherichia coli Proteins / metabolism
  • Female
  • Immunity, Mucosal
  • Immunization
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Skin / immunology*
  • Skin / metabolism
  • Vaccines / administration & dosage*
  • Vaccines / immunology
  • Vaccines / metabolism
  • Vaccines, Subunit / therapeutic use*
  • Vaccines, Synthetic / therapeutic use*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Neutralizing
  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • RiVax
  • Vaccines
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • heat-labile enterotoxin, E coli