IAI Accepts, published online ahead of print on 29 December 2008

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Infect. Immun. doi:10.1128/IAI.01056-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A capsule polysaccharide conjugate vaccine against diarrheal disease caused by Campylobacter jejuni

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

Dept. of Chemistry, University of Guelph, Guelph, Ontario, Canada N1G 2W1; Dept. of Enteric Diseases, Naval Medical Research Center, Silver Spring, MD 20910; and Naval Medical Research Center Detachment, Lima, Peru

^* To whom correspondence should be addressed. Email: patricia.guerry{at}med.navy.mil.

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, 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 non-reducing 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, 2 to 5 CPSs attached to one CRM₁₉₇. When administered subcutaneously to mice, these vaccines elicited robust immune responses and significantly reduced disease following intranasal challenge with the homologous strains of C. jejuni. The CPS_81-176-CRM₁₉₇ vaccine also provided 100% protection against diarrhea in the New World monkey, Aotus nancymaae, following orogastric challenge with C. jejuni 81-176.