Transcutaneous immunization with tetanus toxoid and mutants of Escherichia coli heat-labile enterotoxin as adjuvants elicits strong protective antibody responses.
In this study, the adjuvanticity of 2 nontoxic derivatives (LTK63 and LTR72) of heat-labile enterotoxin of Escherichia coli (LT) was evaluated and was compared with that of a cytosine phosphodiester-guanine (CpG) motif, after transcutaneous immunization with tetanus toxoid (TT). TT plus LTR72 elicited the strongest antibody responses, compared with those elicited by the other vaccines (TT, TT plus LTK63, TT plus CpG, and TT plus LTK63 plus CpG); it neutralized the toxin and conferred full protection after passive transfer in mice. Preexisting immunity to LT mutants did not adversely affect their adjuvant potency. Both LTK63 and LTR72 promoted the induction of IgG1 antibodies. In contrast, mice receiving either CpG motif alone or CpG motif plus LTK63 produced strong IgG2a anti-TT antibody responses. Overall, these findings demonstrate that mutants of enterotoxins with reduced toxicity are effective adjuvants for transcutaneous immunization.
Tierney
Rob
R
Division of Bacteriology, National Institute for Biological Standards and Control, Potters Bar, United Kingdom.
Beignon
Anne-Sophie
AS
Rappuoli
Rino
R
Muller
Sylviane
S
Sesardic
Dorothea
D
Partidos
Charalambos D
CD
D000276:Adjuvants, Immunologic; D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D029968:Escherichia coli Proteins; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D013742:Tetanus / Q000517:prevention & control; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; C027538:heat-labile enterotoxin, E coli