Comparative Adjuvant Effects of Type II Heat-Labile Enterotoxins in Combination with Two Different Candidate Ricin Toxin Vaccine Antigens.

Abstract

Type II heat-labile enterotoxins (HLTs) constitute a promising set of adjuvants that have been shown to enhance humoral and cellular immune responses when coadministered with an array of different proteins, including several pathogen-associated antigens. However, the adjuvant activities of the four best-studied HLTs, LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc, have never been compared side by side. We therefore conducted immunization studies in which LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc were coadministered by the intradermal route to mice with two clinically relevant protein subunit vaccine antigens derived from the enzymatic A subunit (RTA) of ricin toxin, RiVax and RVEc. The HLTs were tested with low and high doses of antigen and were assessed for their abilities to stimulate antigen-specific serum IgG titers, ricin toxin-neutralizing activity (TNA), and protective immunity. We found that all four HLTs tested were effective adjuvants when coadministered with RiVax or RVEc. LT-IIa was of particular interest because as little as 0.03 μg when coadministered with RiVax or RVEc proved effective at augmenting ricin toxin-specific serum antibody titers with nominal evidence of local inflammation. Collectively, these results justify the need for further studies into the mechanism(s) underlying LT-IIa adjuvant activity, with the long-term goal of evaluating LT-IIa's activity in humans.

• Authors: David J Vance, Christopher J Greene, Yinghui Rong, Lorrie M Mandell, Terry D Connell, Nicholas J Mantis
• Journal: Clinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 22 Issue 12 Pg. 1285-93 (Dec 2015) ISSN: 1556-679X [Electronic] United States
• PMID: 26491037 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Chemical References

• Adjuvants, Immunologic
• Antibodies, Neutralizing
• Antigens, Bacterial
• Bacterial Toxins
• Enterotoxins
• Escherichia coli Proteins
• Immunoglobulin G
• RiVax
• Vaccines
• Ricin
• heat-labile enterotoxin, E coli

Topics

• Adjuvants, Immunologic (chemistry)
• Administration, Intranasal
• Animals
• Antibodies, Neutralizing (blood)
• Antigens, Bacterial (administration & dosage, immunology)
• Bacterial Toxins (administration & dosage, immunology)
• Enterotoxigenic Escherichia coli (chemistry)
• Enterotoxins (administration & dosage, immunology)
• Escherichia coli Proteins (administration & dosage, immunology)
• Immunoglobulin G (blood)
• Injections, Intradermal
• Mice
• Ricin (chemistry, immunology)
• Vaccines (administration & dosage, immunology)