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Infection and Immunity, March 2009, p. 1128-1136, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01056-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Capsule Polysaccharide Conjugate Vaccine against Diarrheal Disease Caused by Campylobacter jejuni{triangledown} ,{dagger}

Mario A. Monteiro,1 Shahida Baqar,2 Eric R. Hall,3 Yu-Han Chen,1 Chad K. Porter,2 David E. Bentzel,3 Lisa Applebee,2 and Patricia Guerry2*

Dept. of Chemistry, University of Guelph, Guelph, Ontario, Canada N1G 2W1,1 Dept. of Enteric Diseases, Naval Medical Research Center, Silver Spring, Maryland 20910,2 Naval Medical Research Center Detachment, Lima, Peru3

Received 25 August 2008/ Returned for modification 31 October 2008/ Accepted 20 December 2008

The capsule polysaccharide (CPS) of Campylobacter jejuni is one of the few identified virulence determinants of this important human pathogen. Since CPS conjugate vaccines have been so effective against other mucosal pathogens, we evaluated this approach using CPSs from two strains of C. jejuni, 81-176 (HS23 and HS36 serotype complex) and CG8486 (HS4 serotype complex). The CPSs of 81-176 and CG8486 were independently linked to the carrier protein CRM197 by reductive amination between an aldehyde(s), strategically created at the nonreducing end of each CPS, and accessible amines of CRM197. In both cases, the CPS:CRM197 ratio used was 2:1 by weight. Mass spectrometry and gel electrophoresis showed that on average, each glycoconjugate preparation contained, at least in part, two to five CPSs attached to one CRM197. When administered subcutaneously to mice, these vaccines elicited robust immune responses and significantly reduced the disease following intranasal challenge with the homologous strains of C. jejuni. The CPS81-176-CRM197 vaccine also provided 100% protection against diarrhea in the New World monkey Aotus nancymaae following orogastric challenge with C. jejuni 81-176.

* Corresponding author. Mailing address: Enteric Diseases Department, Naval Medical Research Center, 503 Robert Grant Ave., Silver Spring, MD 20910. Phone: (301) 319-7662. Fax: (301) 319-7679. E-mail: patricia.guerry{at}med.navy.mil

{triangledown} Published ahead of print on 29 December 2008.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: V. J. DiRita

Infection and Immunity, March 2009, p. 1128-1136, Vol. 77, No. 3
0019-9567/09/$08.00+0     doi:10.1128/IAI.01056-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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