title: Transcutaneous immunization with cross-reacting material CRM(197) of diphtheria toxin boosts functional antibody levels in mice primed parenterally with adsorbed diphtheria toxoid vaccine.
abstract: Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM(197)) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM(197) significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM(197) alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM(197) protein. These findings highlight the promising prospect of using booster administrations of CRM(197) via the transcutaneous route to establish good herd immunity against diphtheria.
authors.affiliation: Division of Bacteriology, National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Stickings
authors.forename: Marisa
authors.initials: M
authors.lastname: Peyre
authors.forename: Laura
authors.initials: L
authors.lastname: Coombes
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Charalambos D
authors.initials: CD
authors.lastname: Partidos
authors.forename: Dorothea
authors.initials: D
authors.lastname: Sesardic
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000276:immunology*; D002522:Chlorocebus aethiops; D004165:Diphtheria / Q000276:immunology; D004168:Diphtheria Toxoid / Q000008:administration & dosage* / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D014709:Vero Cells
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D004168:Diphtheria Toxoid; D007074:Immunoglobulin G; C028581:CRM197 (non-toxic variant of diphtheria toxin)