This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McKenzie, R.
Right arrow Articles by Sack, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McKenzie, R.
Right arrow Articles by Sack, D. A.

 Previous Article  |  Next Article 

Infection and Immunity, February 2006, p. 994-1000, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.994-1000.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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

Robin McKenzie,1* A. Louis Bourgeois,1 Fayette Engstrom,1 Eric Hall,2 H. Sunny Chang,1 Joseph G. Gomes,1 Jennifer L. Kyle,1 Fred Cassels,3 Arthur K. Turner,4,{dagger} Roger Randall,4 Michael Darsley,4,{ddagger} Cynthia Lee,5 Philip Bedford,4 Janet Shimko,1,§ and David A. Sack1,||

Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Baltimore, Maryland 21205,1 Navy Medical Research Center, Silver Spring, Maryland,2 Walter Reed Army Institute of Research, Silver Spring, Maryland,3 Acambis Research, Ltd., 100 Fulbourn Rd., Cambridge CB1 9PT, United Kingdom,4 Acambis, Inc., Cambridge, Massachusetts5

Received 6 July 2005/ Returned for modification 23 August 2005/ Accepted 27 October 2005

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.

* Corresponding author. Mailing address: Center for Immunization Research, Department of International Health, Johns Hopkins University, Bloomberg School of Public Health, 624 N. Broadway, HH, Rm. 203, Baltimore, MD 21205. Phone: (410) 502-7450. Fax: (410) 502-6898. E-mail: rmckenz{at}jhmi.edu.

Editor: J. D. Clements

{dagger} Present address: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom.

{ddagger} Present address: Cambridge Biostability, NIAB, Huntingdon Rd., Cambridge CB3 0LE, United Kingdom.

§ Present address: Division of Microbiology and Infectious Diseases, NIAID, NIH, Bethesda, Md.

|| Present address: International Center of Diarrheal Disease Research, Dhaka, Bangladesh.

Infection and Immunity, February 2006, p. 994-1000, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.994-1000.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Daley, A., Randall, R., Darsley, M., Choudhry, N., Thomas, N., Sanderson, I. R, Croft, N. M, Kelly, P. (2007). Genetically modified enterotoxigenic Escherichia coli vaccines induce mucosal immune responses without inflammation. Gut 56: 1550-1556 [Abstract] [Full Text]  
  • Qadri, F., Ahmed, T., Ahmed, F., Bhuiyan, M. S., Mostofa, M. G., Cassels, F. J., Helander, A., Svennerholm, A.-M. (2007). Mucosal and Systemic Immune Responses in Patients with Diarrhea Due to CS6-Expressing Enterotoxigenic Escherichia coli. Infect. Immun. 75: 2269-2274 [Abstract] [Full Text]  
  • Turner, A. K., Beavis, J. C., Stephens, J. C., Greenwood, J., Gewert, C., Thomas, N., Deary, A., Casula, G., Daley, A., Kelly, P., Randall, R., Darsley, M. J. (2006). Construction and Phase I Clinical Evaluation of the Safety and Immunogenicity of a Candidate Enterotoxigenic Escherichia coli Vaccine Strain Expressing Colonization Factor Antigen CFA/I. Infect. Immun. 74: 1062-1071 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»