Abstract
We assessed serologic responses to an oral, killed whole-cell enterotoxigenic Escherichia coli plus cholera toxin B-subunit (ETEC-rCTB) vaccine in 73 Egyptian adults, 105 schoolchildren, and 93 preschool children. Each subject received two doses of vaccine or placebo 2 weeks apart, giving blood before immunization and 7 days after each dose. Plasma antibodies to rCTB and four vaccine-shared colonization factors (CFs) were measured by enzyme-linked immunosorbent assay. Immunoglobulin A (IgA) antibodies to rCTB and CFA/I were measured in all subjects, and those against CS1, CS2, and CS4 were measured in all children plus a subset of 33 adults. IgG antibodies to these five antigens were measured in a subset of 30 to 33 subjects in each cohort. Seroconversion was defined as a >2-fold increase in titer after vaccination. IgA and IgG seroconversion to rCTB was observed in 94 to 95% of adult vaccinees, with titer increases as robust as those previously reported for these two pediatric cohorts. The proportion showing IgA seroconversion to each CF antigen among vaccinated children (range, 70 to 96%) and adults (31 to 69%), as well as IgG seroconversion in children (44 to 75%) and adults (25 to 81%), was significantly higher than the corresponding proportion in placebo recipients, except for IgA responses to CS2 in adults. IgA anti-CF titers peaked after one dose in children, whereas in all age groups IgG antibodies rose incrementally after each dose. Independently, both preimmunization IgA titer and age were inversely related to the magnitude of IgA responses. In conclusion, serologic responses to the ETEC-rCTB vaccine may serve as practical immune outcome measures in future pediatric trials in areas where ETEC is endemic.
MeSH Terms
Administration, Oral
Adult
Antibodies, Bacterial/blood
Bacterial Proteins/immunology
Bacterial Vaccines/immunology
Child
Child, Preschool
Cholera Toxin/immunology
Escherichia coli/immunology
Fimbriae Proteins
Humans
Immunoglobulin A/blood
Immunoglobulin G/blood
Middle Aged
Vaccines, Synthetic/immunology
Chemicals
Antibodies, Bacterial
Bacterial Proteins
Bacterial Vaccines
Immunoglobulin A
Immunoglobulin G
Vaccines, Synthetic
colonization factor antigens
Fimbriae Proteins
Cholera Toxin
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Hall E R
U.S. Naval Medical Research Unit No. Three, Cairo, Egypt.
Wierzba T F
Ahrén C
Rao M R
Bassily S
Francis W
Girgis F Y
Safwat M
Lee Y J
Svennerholm A M
Clemens J D
Savarino S J
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