{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:09:51Z","timestamp":1791407391986,"version":"4.3.3"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            A vaccine against enterotoxigenic\n            <jats:italic>Escherichia coli<\/jats:italic>\n            (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 \u00d7 10\n            <jats:sup>9<\/jats:sup>\n            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% (\n            <jats:italic>P<\/jats:italic>\n            = 0.01) for anti-CFA\/II IgA-ASCs, 55% versus 30% (\n            <jats:italic>P<\/jats:italic>\n            = 0.11) for serum anti-CS1 IgA by TRF, and 65% versus 25% (\n            <jats:italic>P<\/jats:italic>\n            = 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 (\n            <jats:italic>P<\/jats:italic>\n            \u2009= 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.\n          <\/jats:p>","DOI":"10.1128\/iai.74.2.994-1000.2006","type":"journal-article","created":{"date-parts":[[2006,1,21]],"date-time":"2006-01-21T01:42:38Z","timestamp":1137807758000},"page":"994-1000","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":32,"title":["Comparative Safety and Immunogenicity of Two Attenuated Enterotoxigenic\n            <i>Escherichia coli<\/i>\n            Vaccine Strains in Healthy Adults"],"prefix":"10.1128","volume":"74","author":[{"given":"Robin","family":"McKenzie","sequence":"first","affiliation":[{"name":"Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Baltimore, Maryland 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Louis","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Baltimore, Maryland 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayette","family":"Engstrom","sequence":"additional","affiliation":[{"name":"Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Baltimore, Maryland 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hall","sequence":"additional","affiliation":[{"name":"Navy Medical Research Center, Silver Spring, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. Sunny","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Baltimore, Maryland 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph G.","family":"Gomes","sequence":"additional","affiliation":[{"name":"Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Baltimore, Maryland 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Kyle","sequence":"additional","affiliation":[{"name":"Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Baltimore, Maryland 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Cassels","sequence":"additional","affiliation":[{"name":"Walter Reed Army Institute of Research, Silver Spring, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur K.","family":"Turner","sequence":"additional","affiliation":[{"name":"Acambis Research, Ltd., 100 Fulbourn Rd., Cambridge CB1 9PT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Randall","sequence":"additional","affiliation":[{"name":"Acambis Research, Ltd., 100 Fulbourn Rd., Cambridge CB1 9PT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Darsley","sequence":"additional","affiliation":[{"name":"Acambis Research, Ltd., 100 Fulbourn Rd., Cambridge CB1 9PT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Lee","sequence":"additional","affiliation":[{"name":"Acambis, Inc., Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Bedford","sequence":"additional","affiliation":[{"name":"Acambis Research, Ltd., 100 Fulbourn Rd., Cambridge CB1 9PT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Shimko","sequence":"additional","affiliation":[{"name":"Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 N. 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M. 1986. Fimbriae (pili) as vaccines, p. 143-145. In D. L. Lark (ed.), Protein-carbohydrate interactions in biological systems: the molecular biology of microbial pathogenicity. 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