The Pediatric Infectious Disease Journal
Original Studies
Introductory evaluation of an oral, killed whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Egyptian infants
SAVARINO, STEPHEN J. MD, MPH*; HALL, ERIC R. PhD*; BASSILY, SAMIR MBBCH; WIERZBA, THOMAS F. PhD; YOUSSEF, FOUAD G. MBBCH, PhD; PERUSKI, LEONARD F. JR. PhD†; ABU-ELYAZEED, REMON MD, PhD; RAO, MALLA MENG; FRANCIS, WAGDY M. PhD; EL MOHAMADY, HANAN PhD; SAFWAT, MOHAMMED MBBCH; NAFICY, ABDOLLAH B. MD; SVENNERHOLM, ANN-MARI MD, PhD; JERTBORN, MARIANNE MD; LEE, YOUNG J. PhD‡; CLEMENS, JOHN D. MD§ FOR THE PRIDE STUDY GROUP
From US Naval Medical Research Unit Number 3, Cairo (SJS, ERH, SM, TDW, FGY, LFP, RAE, WMF, HEM), and Egyptian Ministry of Health and Population, Banhâ, al-Qalyûbîyah Governorate (MS), Egypt; the Division of Epidemiology, Statistics and Prevention Research, National Institute of Child Health and Human Development, Bethesda, MD (MR, ABN, YJL, JDC); the Department of Medical Microbiology and Immunology, University of Göteborg, Sweden (AS, MJ); and International Vaccine Institute, Seoul, Korea (JDC).
Accepted for publication Nov. 19, 2001.
*Current address: Enteric Diseases Department, US Naval Medical Research Center, Silver Spring, MD.
†Current address: Biologic Defense Research Directorate, US Naval Medical Research Center, Silver Spring, MD.
‡Current address: WESTAT-Korea, Seoul, Korea.
§Current address: International Vaccine Institute, Seoul, Korea.
Address for reprints: Captain Stephen J. Savarino, US Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910. Fax 301-319-7679; E-mail [email protected].
The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Navy Department, Department of Defense, the US Government or the Egyptian Ministry of Health and Population.
Abstract
Background.
We conducted the first trial to assess the safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B-subunit vaccine in children <2 years old.
Methods.
Three doses of vaccine or killed E. coli K-12 control were given at 2-week intervals to 64 Egyptian infants, 6 to 18 months old, in a randomized, double blind manner. Adverse events were monitored for 3 days after each dose. Blood was collected before immunization and 7 to 10 days after each dose to assess vaccine-specific serologic responses.
Results.
There was no statistically significant intergroup difference in the percentage of subjects reporting the primary safety endpoint (diarrhea or vomiting) after the first (31%, vaccine; 30%, control) or third (14%, vaccine; 18%, control) dose, whereas there was a trend toward greater reporting in the vaccine group after Dose 2 (36%, vaccine; 18%, control;P = 0.052). The percentage of children showing IgA seroconversion after any dose was higher in the vaccine than the control group for recombinant cholera toxin B-subunit (97%vs. 46%), colonization factor antigen I (61%vs. 18%) and coli surface antigen 4 (39%vs. 4%) (P < 0.001 for each comparison). IgG seroconversion rates in the vaccine and control groups were 97 and 21% to recombinant cholera toxin B-subunit (P < 0.001), 64 and 29% for colonization factor antigen I (P < 0.01), 53 and 21% for coli surface antigen 2 (P < 0.05) and 58 and 4% for coli surface antigen 4 (P < 0.001), respectively. The third vaccine dose was followed by augmented IgG antitoxin titers.
Conclusion.
The oral enterotoxigenic E. coli vaccine was safe and immunogenic in this setting in Egyptian infants.