Comparative Adjuvant Effects of Type II Heat-Labile Enterotoxins in Combination with Two Different Candidate Ricin Toxin Vaccine Antigens.
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.
Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
David J
http://orcid.org/0000-0002-9913-7722
DJ
Vance
Department of Microbiology and Immunology and The Witebsky Center for Microbial Pathogenesis and Immunology, The University at Buffalo, Buffalo, New York, USA.
Christopher J
CJ
Greene
Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
Yinghui
Y
Rong
Department of Microbiology and Immunology and The Witebsky Center for Microbial Pathogenesis and Immunology, The University at Buffalo, Buffalo, New York, USA.
Lorrie M
LM
Mandell
Department of Microbiology and Immunology and The Witebsky Center for Microbial Pathogenesis and Immunology, The University at Buffalo, Buffalo, New York, USA.
Terry D
TD
Connell
Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York, USA Department of Biomedical Sciences, University at Albany School of Public Health, Albany, New York, USA nicholas.mantis@health.ny.gov.
Nicholas J
http://orcid.org/0000-0002-5083-8640
NJ
Mantis
D000276:Adjuvants, Immunologic / Q000737:chemistry; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology*; D054307:Enterotoxigenic Escherichia coli / Q000737:chemistry; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000008:administration & dosage / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood*; D007271:Injections, Intradermal; D051379:Mice; D012276:Ricin / Q000737:chemistry / Q000276:immunology*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; C509236:RiVax; D014612:Vaccines; D012276:Ricin; C027538:heat-labile enterotoxin, E coli