Serologic Correlates of Protection against Enterotoxigenic Escherichia coli Diarrhea
1Division of Epidemiology, Statistics, and Prevention Research, National Institute of Child Health and Human Development, Bethesda, and 2US Naval Medical Research Center, Silver Spring, Maryland; 3US Naval Medical Research Unit No. 3, Cairo, Egypt; 4Department of Medical Microbiology and Immunology, Göteborg University, Göteborg, Sweden; 5International Vaccine Institute, Seoul, South Korea
Background.
We conducted a nested case‐control study in 397 rural Egyptian children <36 months of age to assess the correlation between serum levels of antibodies against toxin and colonization factors (CFs) and the risk of homologous enterotoxigenic Escherichia coli (ETEC) diarrhea.
Methods.Active case detection was performed via semiweekly home visits, and blood was obtained at 3‐month intervals. After each serosurvey, case subjects were selected from children experiencing a CF antigen (CFA)/I–, CFA/II‐, CFA/IV‐, or heat‐labile enterotoxin (LT)–ETEC diarrheal episode during the subsequent 3 months. Up to 5 control subjects per case subject were selected from children who did not experience an ETEC diarrheal episode during the corresponding interval. Serum titers of immunoglobulin G antibodies against CFA/I, coli surface antigen (CS) 3, CS6, and LT were measured by enzyme‐linked immunosorbant assay.
Results.The distribution of serum titers of LT, CS3, and CS6 antibodies did not differ between the case and control subjects. For children <18 months of age, serum titers of CFA/I antibody were inversely related to the risk of CFA/I‐ETEC diarrhea; reciprocal serum titers of CFA/I antibody 
76 were associated with a 77% reduction in the odds of CFA/I‐ETEC diarrhea.
Conclusion.Induction of reciprocal serum titers of antibodies against CFA/I within or above the 76–186 range should be further evaluated as a predictor for assessment of the ability of candidate vaccines to protect against CFA/I‐ETEC diarrhea.
Received 21 July 2004; accepted 8 September 2004; electronically published 14 January 2005.
Cited by
Online publication date: 1-Sep-2008.
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Online publication date: 1-Jun-2008.
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Financial support: Naval Medical Research and Development Command (Work Unit No. B69000101.PIX.3270); National Institute of Child Health and Human Development Interagency (agreement Y1‐HD‐0026‐01); World Health Organization Global Programme for Vaccines and Immunization/Vaccine Research and Development.
The opinions and assertions contained here are the private ones of the authors and are not to be construed as official or reflecting the views of the Navy Department, the Department of Defense, the US Government, or the Egyptian Ministry of Health and Population.
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M.R.R. and T.F.W. contributed equally to this work.
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Present affiliations: Parasitology and International Program Branch, Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (M.R.R. and A.N.); Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, Georgia (T.F.W.); Enteric Diseases Department, Naval Medical Research Center, Bethesda, Maryland (S.J.S.); GlaxoSmithKline, Singapore (R.A.‐E.).