Murine antibody response to intranasally administered enterotoxigenic Escherichia coli colonization factor CS6.
Enterotoxigenic Escherichia coli (ETEC) is the most common cause of bacterial diarrhea worldwide and is an important cause of infant morbidity and mortality in developing nations. ETEC colonization factors (CF) are virulence determinants that appear to be protective antigens in humans and are the major target of vaccine efforts. One of the most prevalent CF, CS6, is expressed by about 30% of ETEC worldwide. This study was designed to compare the immunogenicity between encapsulated CS6 (CS6-PLG) and unencapsulated CS6. Recombinant CS6 was purified and encapsulated in biodegradable poly(DL-lactide-co-glycolide) (PLG) microspheres using current Good Manufacturing Practices (cGMP). CS6-PLG and CS6 were administered intranasally (IN) to BALB/c mice in three vaccinations 4 weeks apart. Enzyme linked immunosorbent assay (ELISA) was used to measure the anti-CS6 response in serum and mucosal secretions following each of the three inoculations. Mice vaccinated with two or three doses of CS6-PLG demonstrated a significantly greater rise in serum anti-CS6 IgG and mucosal IgA titer values than those immunized with two or three doses of CS6 alone. Three doses of CS6-PLG led to anti-CS6 serum IgG and mucosal IgA titer values 14-fold and 4.4-fold greater, respectively, than three doses of CS6 (P<0.02). IN administered CS6 to mice is safe and highly immunogenic either alone or when encapsulated in microspheres. PLG microsphere encapsulation of CS6 significantly augments the antibody response to that antigen when administered to a mucosal surface.
Division of Pediatric Gastroenterology and Nutrition, Walter Reed Army Medical Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Arthur J
AJ
de Lorimier
Wyatt
W
Byrd
Eric R
ER
Hall
William M
WM
Vaughan
Douglas
D
Tang
Zachary J
ZJ
Roberts
Charles E
CE
McQueen
Frederick J
FJ
Cassels
D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D001835:Body Weight; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control; D036781:Fimbriae Proteins / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice
D001428:Bacterial Vaccines; D007074:Immunoglobulin G; C022924:colonization factor antigens; D036781:Fimbriae Proteins