Comparative safety and immunogenicity of two attenuated enterotoxigenic Escherichia coli vaccine strains in healthy adults

Robin McKenzie, Louis Bourgeois, Fayette Engstrom, Eric Hall, H. Sunny Chang, Joseph G. Gomes, Jennifer L. Kyle, Fred Cassels, Arthur K. Turner, Roger Randall, Michael Darsley, Cynthia Lee, Philip Bedford, Janet Shimko, David A. Sack

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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 × 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.

Original languageEnglish (US)
Pages (from-to)994-1000
Number of pages7
JournalInfection and immunity
Issue number2
StatePublished - Feb 2006

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases


Dive into the research topics of 'Comparative safety and immunogenicity of two attenuated enterotoxigenic Escherichia coli vaccine strains in healthy adults'. Together they form a unique fingerprint.

Cite this