Safety and immunogenicity of a prototype enterotoxigenic Escherichia coli vaccine administered transcutaneously.
Transcutaneous immunization (TCI) is a new method for vaccine delivery that has been shown to induce immunity relevant to enteric disease vaccines. We evaluated the clinical safety and immunogenicity of a recombinant subunit vaccine against enterotoxigenic Escherichia coli (ETEC) delivered by TCI. Adult volunteers received patches containing the recombinant ETEC colonization factor CS6, either with heat-labile enterotoxin (LT) or patches containing CS6 alone. The vaccine was administered at 0, 1, and 3 months, and serum antibodies and antibody-secreting cells (ASCs) were assessed. Among the 26 volunteers that completed the trial, there were no responses to CS6 in the absence of LT. In the groups receiving both CS6 and LT, 68 and 53% were found to have serum anti-CS6 immunoglobulin G (IgG) and IgA, respectively; 37 and 42% had IgG and IgA anti-CS6 ASCs. All of the volunteers receiving LT had anti-LT IgG, and 90% had serum anti-LT IgA; 79 and 37% had anti-LT IgG and IgA ASCs. Delayed-type hypersensitivity (DTH), suggesting T-cell responses, was seen in 14 of 19 volunteers receiving LT and CS6; no DTH was seen in subjects receiving CS6 alone. This study demonstrated that protein antigens delivered by a simple patch could induce significant systemic immune responses but only in the presence of an adjuvant such as LT. The data suggest that an ETEC vaccine for travelers delivered by a patch may be a viable approach worthy of further evaluation.
Güereña-Burgueño
Fernando
F
Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500, USA. Fernando.Guerena@NA.AMEDD.ARMY.MIL
Hall
Eric R
ER
Taylor
David N
DN
Cassels
Frederick J
FJ
Scott
Daniel A
DA
Wolf
Marcia K
MK
Roberts
Zachary J
ZJ
Nesterova
Galina V
GV
Alving
Carl R
CR
Glenn
Gregory M
GM
D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000921:Antibody-Producing Cells / Q000502:physiology; D000942:Antigens, Bacterial; D000954:Antigens, Surface / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D003967:Diarrhea / Q000517:prevention & control; D004768:Enterotoxins / Q000276:immunology*; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D008297:Male; D008875:Middle Aged
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; C027538:heat-labile enterotoxin, E coli