Transcutaneous immunization using colonization factor and heat-labile enterotoxin induces correlates of protective immunity for enterotoxigenic Escherichia coli.
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.
Yu
Jianmei
J
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Cassels
Frederick
F
Scharton-Kersten
Tanya
T
Hammond
Scott A
SA
Hartman
Antoinette
A
Angov
Evelina
E
Corthésy
Blaise
B
Alving
Carl
C
Glenn
Gregory
G
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
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