Journal Mobile Options
Table of Contents
Vol. 91, No. 2, 2007
Issue release date: February 2007
Neonatology 2007;91:114–120

The Potential Salmonella aroA Vaccine Strain Is Safe and Effective in Young BALB/c Mice

Burns-Guydish S.M. · Zhao H. · Stevenson D.K. · Contag C.H.
aDivision of Neonatal and Developmental Medicine, Department of Pediatrics, and bDepartments of Microbiology and Immunology, and Radiology, Stanford University School of Medicine, Stanford, Calif., USA

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Due to the increased susceptibility of neonates to pathogens including those with mutations, the use of live vaccine strategies in the human population may present a potential risk to the young. Objectives: The specific aim of this study was to assess the risk that prospective Salmonella enterica serovar Typhimurium vaccine strains pose for the neonate and determine whether the strains are an effective vaccine by assessing the adaptive immune response. Methods: To evaluate the susceptibility of young mice to potential vaccine strains, S. typhimuriumaroA and ΔphoP mutant strains were labeled by chromosomal insertion of the lux operon – this serves as a readily traceable marker of infection using noninvasive imaging methods. BALB/c mice ages 1, 2, 4, and 6 weeks of age were fed the bioluminescent aroA or ΔphoP strains and the course of infection was monitored by in vivobioluminescence imaging. In addition, blood samples were collected post-inoculation to assess the IgG response of mice to S. typhimurium LPS. Results: Young BALB/c mice were not susceptible to the aroA strain in contrast to their susceptibility to the ΔphoP strain at a dose of 109 colony forming units. Delivery by oral feeding of the aroA and ΔphoP strains in young mice also produced a robust IgG anti-LPS response. Conclusion: Here, we report that young 2-week-old mice orally fed the bioluminescent aroAS. typhimurium strain were not susceptible to infection and elicited a protective immune response.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Santos RL, Zhang S, Tsolis RM, Kingsley RA, Adams LG, Baumler AJ: Animal models of Salmonella infections: enteritis versus typhoid fever. Microbes Infect 2001;3:1335–1344.
  2. Blaser MJ, Feldman RA: From the centers for disease control. Salmonella bacteremia: reports to the Centers for Disease Control, 1968–1979. J Infect Dis 1981;143:743–746.
  3. Pasetti MF, Levine MM, Sztein MB: Animal models paving the way for clinical trials of attenuated Salmonella enterica serovar Typhi live oral vaccines and live vectors. Vaccine 2003;21:401–418.
  4. Niethammer AG, Xiang R, Becker JC, Wodrich H, Pertl U, Karsten G, Eliceiri BP, Reisfeld RA: A DNA vaccine against VEGF receptor 2 prevents effective angiogenesis and inhibits tumor growth. Nat Med 2002;8:1369–1375.
  5. Capozzo AV, Cuberos L, Levine MM, Pasetti MF: Mucosally delivered Salmonella live vector vaccines elicit potent immune responses against a foreign antigen in neonatal mice born to naive and immune mothers. Infect Immun 2004;72:4637–4646.
  6. Burns-Guydish SM, Olomu IN, Zhao H, Wong RJ, Stevenson DK, Contag CH: Monitoring age-related susceptibility of young mice to oral Salmonella enterica serovar Typhimurium infection using an in vivo murine model. Pediatr Res 2005;58:153–158.
  7. Stocker BA, Hoiseth SK, Smith BP: Aromatic-dependent ‘Salmonella sp.’ as live vaccine in mice and calves. Dev Biol Stand 1983;53:47–54.
  8. Rathman M, Sjaastad MD, Falkow S: Acidification of phagosomes containing Salmonella typhimurium in murine macrophages. Infect Immun 1996;64:2765–2773.
  9. Contag CH, Contag PR, Mullins JI, Spilman SD, Stevenson DK, Benaron DA: Photonic detection of bacterial pathogens in living hosts. Mol Microbiol 1995;18:593–603.
  10. Winson MK, Swift S, Hill PJ, Sims CM, Griesmayr G, Bycroft BW, Williams P, Stewart GS: Engineering the luxCDABE genes from Photorhabdus luminescens to provide a bioluminescent reporter for constitutive and promoter probe plasmids and mini-Tn5 constructs. FEMS Microbiol Lett 1998;163:193–202.
  11. Winson MK, Swift S, Fish L, Throup JP, Jorgensen F, Chhabra SR, Bycroft BW, Williams P, Stewart GS: Construction and analysis of luxCDABE-based plasmid sensors for investigating N-acyl homoserine lactone-mediated quorum sensing. FEMS Microbiol Lett 1998;163:185–192.
  12. Miller SI, Kukral AM, Mekalanos JJ: A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci USA 1989;86:5054–5058.
  13. Tacket CO, Kelly SM, Schodel F, Losonsky G, Nataro JP, Edelman R, Levine MM, Curtiss R, 3rd: Safety and immunogenicity in humans of an attenuated Salmonella typhi vaccine vector strain expressing plasmid-encoded hepatitis B antigens stabilized by the Asd-balanced lethal vector system. Infect Immun 1997;65:3381–3385.
  14. Pasetti MF, Pickett TE, Levine MM, Sztein MB: A comparison of immunogenicity and in vivo distribution of Salmonella enterica serovar Typhi and Typhimurium live vector vaccines delivered by mucosal routes in the murine model. Vaccine 2000;18:3208–3213.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50