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Infection and Immunity, April 2000, p. 2161-2166, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Clostridium difficile Recombinant Toxin A Repeating Units as a Carrier Protein for Conjugate Vaccines: Studies of Pneumococcal Type 14, Escherichia coli K1, and Shigella flexneri Type 2a Polysaccharides in Mice

Danka Pavliakova,¹ J. Scott Moncrief,² David M. Lyerly,² Gerald Schiffman,³ Dolores A. Bryla,¹ John B. Robbins,¹ and Rachel Schneerson^1,*

National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland¹; Techlab, Inc., Blacksburg, Virginia²; and Downstate Medical Center, State University of New York, Brooklyn, New York³

Received 28 September 1999/Returned for modification 8 December 1999/Accepted 18 January 2000

Unlike the native protein, a nontoxic peptide (repeating unit of the native toxin designated rARU) from Clostridium difficile toxin A (CDTA) afforded an antigen that could be bound covalently to the surface polysaccharides of pneumococcus type 14, Shigella flexneri type 2a, and Escherichia coli K1. The yields of these polysaccharide-protein conjugates were significantly increased by prior treatment of rARU with succinic anhydride. Conjugates, prepared with rARU or succinylated (rARUsucc), were administered to mice by a clinically relevant dosage and immunization scheme. All conjugates elicited high levels of serum immunoglobulin G both to the polysaccharides and to CDTA. Conjugate-induced anti-CDTA had neutralizing activity in vitro and protected mice challenged with CDTA, similar to the rARU alone. Conjugates prepared with succinylated rARU, therefore, have potential for serving both as effective carrier proteins for polysaccharides and for preventing enteric disease caused by C. difficile.

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^* Corresponding author. Mailing address: National Institutes of Health, Building 6, Room 424, Bethesda, MD 20892. Phone: (301) 496-1185. Fax: (301) 402-9108. E-mail: schneerr{at}exchange.nih.gov.

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Infection and Immunity, April 2000, p. 2161-2166, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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