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 elicit...

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Bibliographic Details
Published in:The Journal of infectious diseases 2003-09, Vol.188 (5), p.753-758
Main Authors: Tierney, Rob, Beignon, Anne-Sophie, Rappuoli, Rino, Muller, Sylviane, Sesardic, Dorothea, Partidos, Charalambos D.
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Administration, Cutaneous
Animals
Antibodies
Antibodies, Bacterial - blood
Antigens
Bacteria
Bacterial Toxins - genetics
Bacterial Toxins - immunology
Bacteriology
Biological and medical sciences
Clostridium tetani
CpG Islands - immunology
Enterotoxins
Enterotoxins - genetics
Enterotoxins - immunology
Enzyme linked immunosorbent assay
Escherichia coli
Escherichia coli - genetics
Escherichia coli - immunology
Escherichia coli - metabolism
Escherichia coli Proteins
Female
Fundamental and applied biological sciences. Psychology
Immunization
Immunoglobulin G - blood
Mice
Mice, Inbred BALB C
Microbiology
Mutation
Skin
Tetanus
Tetanus - prevention & control
Tetanus Toxoid - administration & dosage
Tetanus Toxoid - immunology
Toxins
Vaccination
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
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Summary: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
ISSN:0022-1899
1537-6613
DOI:10.1086/377287