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

• Published in: Clinical and vaccine immunology Vol. 22; no. 12; pp. 1285 - 1293
• Main Authors: Vance, David J, Greene, Christopher J, Rong, Yinghui, Mandell, Lorrie M, Connell, Terry D, Mantis, Nicholas J
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.12.2015
• Subjects: Adjuvants, Immunologic - chemistry; Administration, Intranasal; Animals; Antibodies, Neutralizing - blood; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - immunology; Bacterial Toxins - administration & dosage; Bacterial Toxins - immunology; Enterotoxigenic Escherichia coli - chemistry; Enterotoxins - administration & dosage; Enterotoxins - immunology; Escherichia coli Proteins - administration & dosage; Escherichia coli Proteins - immunology; Immunoglobulin G - blood; Injections, Intradermal; Mice; Ricin - chemistry; Ricin - immunology; Vaccines; Vaccines - administration & dosage; Vaccines - immunology
• ISSN: 1556-6811; 1556-679X
• DOI: 10.1128/CVI.00402-15

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.