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 Cripps, A. W.
Right arrow Articles by Sedlak-Weinstein, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cripps, A. W.
Right arrow Articles by Sedlak-Weinstein, L.

 Previous Article  |  Next Article 

Infection and Immunity, February 2006, p. 968-974, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.968-974.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Safety and Immunogenicity of an Oral Inactivated Whole-Cell Pseudomonas aeruginosa Vaccine Administered to Healthy Human Subjects

Allan W. Cripps,1* Keith Peek,2 Margaret Dunkley,3 Kevin Vento,4 Joanne K. Marjason,5 Madonna E. McIntyre,5 Phil Sizer,2 Duncan Croft,2,{dagger} and Lis Sedlak-Weinstein1

School of Medicine, Griffith University, Queensland, Australia,1 Provalis PLC, Deeside, Flintshire, United Kingdom,2 University of Newcastle, Newcastle, New South Wales, Australia,3 Protein Reference and Immunopathology Unit, St. George's Hospital Medical School, London, United Kingdom,4 Centres for Studies in Drug Disposition, Department of Medicine, Royal Brisbane Hospital, Queensland, Australia5

Received 21 June 2005/ Returned for modification 23 August 2005/ Accepted 27 October 2005

This study examines the safety and immunogenicity of an oral, whole-cell Pseudomonas aeruginosa vaccine administered to healthy volunteers. Thirty subjects received an oral dose of Pseudostat in two timed, measured doses with serological follow-up to 56 days postvaccination. Following vaccination, several individuals were identified as antibody responders for all three immunoglobulin (Ig) isotypes tested, specifically against whole-cell P. aeruginosa extract and outer membrane proteins F and I. The mean pooled lipopolysaccharide antigen-specific IgA showed the most significant and constant increases in titer postdose, with a similar increase in titer for whole-cell P. aeruginosa extract-specific IgA. The results demonstrated an increased phagocytic ability of the selected macrophage cell line in post vaccination sera. Furthermore a significant increase in intracellular macrophage killing of opsonized P. aeruginosa was also demonstrated (82% on day 14 postdose) in the presence of the postvaccination sera. The safety component of the study did not show any vaccine-attributable adverse effects in any of the subjects, as documented by clinical evidence, hematology, and biochemistry profiles. We conclude that Pseudostat is safe and immunogenic in humans at this dose and that further studies to determine the appropriate dosage and efficacy are needed. In our study, we have shown that the most significant and sustained responses to oral vaccination in human adult volunteers were serum IgA levels and that pooled sera collected postimmunization have an increased capacity to promote opsonophagocytotic killing of P. aeruginosa.

* Corresponding author. Mailing address: Griffith Health, Griffith Centre for Medicine and Oral Health, Griffith University, PMB 50, Gold Coast Mail Centre, Queensland 9726, Australia. Phone: 61 7 5678 0709. Fax: 61 7 5678 0795. E-mail: allan.cripps{at}griffith.edu.au.

Editor: J. D. Clements

{dagger} Present address: Teva Pharmaceuticals, Ltd., Aylesbury, Bucks, United Kingdom.

Infection and Immunity, February 2006, p. 968-974, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.968-974.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Perez, F., Hujer, A. M., Hujer, K. M., Decker, B. K., Rather, P. N., Bonomo, R. A. (2007). Global Challenge of Multidrug-Resistant Acinetobacter baumannii. Antimicrob. Agents Chemother. 51: 3471-3484 [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»