title: Transcutaneous immunization using colonization factor and heat-labile enterotoxin induces correlates of protective immunity for enterotoxigenic Escherichia coli.
abstract: Enterotoxigenic Escherichia coli (ETEC) diarrheal disease is a worldwide problem that may be addressed by transcutaneous delivery of a vaccine. In several human settings, protective immunity has been associated with immune responses to E. coli colonization factors and to the heat-labile toxin that induces the diarrhea. In this set of animal studies, transcutaneous immunization (TCI) using recombinant colonization factor CS6 and cholera toxin (CT) or heat-labile enterotoxin (LT) as the adjuvant induced immunoglobulin G (IgG) and IgA anti-CS6 responses in sera and stools and antibody responses that recognized CS6 antigen in its native configuration. The antitoxin immunity induced by TCI was also shown to protect against enteric toxin challenge. Although immunization with LT via the skin induced mucosal secretory IgA responses to LT, protection could also be achieved by intravenous injection of the immune sera. Finally, a malaria vaccine antigen, merzoite surface protein 1(42) administered with CT as the adjuvant, induced both merzoite surface protein antibodies and T-cell responses while conferring protective antitoxin immunity, suggesting that both antiparasitic activity and antidiarrheal activity can be obtained with a single vaccine formulation. Overall, our results demonstrate that relevant colonization factor and antitoxin immunity can be induced by TCI and suggest that an ETEC traveler's diarrhea vaccine could be delivered by using a patch.
authors.affiliation: Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Yu
authors.forename: Frederick
authors.initials: F
authors.lastname: Cassels
authors.forename: Tanya
authors.initials: T
authors.lastname: Scharton-Kersten
authors.forename: Scott A
authors.initials: SA
authors.lastname: Hammond
authors.forename: Antoinette
authors.initials: A
authors.lastname: Hartman
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: Blaise
authors.initials: B
authors.lastname: Corthésy
authors.forename: Carl
authors.initials: C
authors.lastname: Alving
authors.forename: Gregory
authors.initials: G
authors.lastname: Glenn
mesh_terms: D000276:Adjuvants, Immunologic; D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial; D000954:Antigens, Surface / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D003967:Diarrhea / Q000517:prevention & control*; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D004927:Escherichia coli Infections / Q000517:prevention & control*; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D005243:Feces / Q000382:microbiology; D005260:Female; D006168:Guinea Pigs; D007116:Immunization, Passive; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008168:Lung / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology; D014621:Vagina / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000954:Antigens, Surface; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C098406:CS6 antigen, E coli; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C027538:heat-labile enterotoxin, E coli