Comparative Safety and Immunogenicity of Two Attenuated Enterotoxigenic Escherichia coli Vaccine Strains in Healthy Adults

• Published in: Infection and Immunity Vol. 74; no. 2; pp. 994 - 1000
• Main Authors: McKenzie, Robin, Bourgeois, A. Louis, Engstrom, Fayette, Hall, Eric, Chang, H. Sunny, Gomes, Joseph G, Kyle, Jennifer L, Cassels, Fred, Turner, Arthur K, Randall, Roger, Darsley, Michael, Lee, Cynthia, Bedford, Philip, Shimko, Janet, Sack, David A
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for Microbiology 01.02.2006; American Society for Microbiology (ASM)
• Subjects: administration & dosage; Adolescent; Adult; adults; adverse effects; analysis; Antibodies, Bacterial; Antibodies, Bacterial - analysis; Antibodies, Bacterial - blood; Antibody-Producing Cells; Bacteriology; Biological and medical sciences; blood; blood serum; children; colorimetry; developing countries; diarrhea; Double-Blind Method; enterotoxigenic Escherichia coli; Enterotoxins; Enterotoxins - metabolism; enzyme-linked immunosorbent assay; Escherichia coli; Escherichia coli - immunology; Escherichia coli Infections; Escherichia coli Infections - prevention & control; Escherichia coli Vaccines; Escherichia coli Vaccines - administration & dosage; Escherichia coli Vaccines - adverse effects; Escherichia coli Vaccines - immunology; Feces; Feces - microbiology; fluorescence; Fundamental and applied biological sciences. Psychology; Humans; immune response; immunoglobulin A; Immunoglobulin A - analysis; Immunoglobulin A - blood; immunoglobulin G; Immunoglobulin G - blood; immunology; metabolism; Microbial Immunity and Vaccines; Microbiology; Middle Aged; Miscellaneous; prevention & control; Vaccines, Attenuated; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - adverse effects; Vaccines, Attenuated - immunology; Human; Immunogenicity; Microbiology; Vaccine strain; Toxicity; Escherichia coli; Bacteria; Adult; Attenuated strain; Immunity; Enterobacteriaceae
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.74.2.994-1000.2006

A vaccine against enterotoxigenic Escherichia coli (ETEC) is needed to prevent diarrheal illness among children in developing countries and at-risk travelers. Two live attenuated ETEC strains, PTL002 and PTL003, which express the ETEC colonization factor CFA/II, were evaluated for safety and immunogenicity. In a randomized, double-blind, placebo-controlled trial, 19 subjects ingested one dose, and 21 subjects ingested two doses (days 0 and 10) of PTL-002 or PTL-003 at 2 x 10⁹ CFU/dose. Anti-CFA/II mucosal immune responses were determined from the number of antibody-secreting cells (ASC) in blood measured by enzyme-linked immunospot assay, the antibody in lymphocyte supernatants (ALS) measured by enzyme-linked immunosorbent assay (ELISA), and fecal immunoglobulin A (IgA) levels determined by ELISA. Time-resolved fluorescence (TRF) ELISA was more sensitive than standard colorimetric ELISA for measuring serum antibody responses to CFA/II and its components, CS1 and CS3. Both constructs were well tolerated. Mild diarrhea occurred after 2 of 31 doses (6%) of PTL-003. PTL-003 produced more sustained intestinal colonization than PTL-002 and better IgA response rates: 90% versus 55% (P = 0.01) for anti-CFA/II IgA-ASCs, 55% versus 30% (P = 0.11) for serum anti-CS1 IgA by TRF, and 65% versus 25% (P = 0.03) for serum anti-CS3 IgA by TRF. Serum IgG response rates to CS1 or CS3 were 55% in PTL-003 recipients and 15% in PTL-002 recipients (P = 0.02). Two doses of either strain were not significantly more immunogenic than one. Based on its superior immunogenicity, which was comparable to that of a virulent ETEC strain and other ETEC vaccine candidates, PTL-003 will be developed further as a component of a live, oral attenuated ETEC vaccine.