CVI Accepts, published online ahead of print on 4 November 2009

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Clin. Vaccine Immunol. doi:10.1128/CVI.00266-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Physical-chemical Characterization and Immunologic Properties of Salmonella ser. Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates

Changfa Cui^*, Rodney Carbis, So Jung An, Hyun Jang, Cecil Czerkinsky, Shousun C. Szu, and John D. Clemens

International Vaccine Institute, SNU Research Park, San 4-8 Bongcheon-7 Dong, Kwanak-Gu, Seoul, Korea, 151-919; Eunice Kennedy Shriver National Institute of Child Health & Human Development, NIH, Bethesda, MD 20854, USA

^* To whom correspondence should be addressed. Email: ccui{at}ivi.int.

Typhoid fever remains a serious public health problem in the developing countries, especially among young children. Recent studies showed more than 50% of typhoid cases are in children under 5 years old. Licensed vaccines, such as Salmonella ser. Typhi capsular Vi, did not confer protection against typhoid fever for this age group. Vi conjugate, prepared by binding Vi to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), induces protective levels of antibody at as young as 2-years old. Because the lack of regulatory precedent of rEPA in licensing vaccines, we employed diphtheria toxoid (DT) as the carrier protein to accommodate the accessibility in developing countries. Five lots of Vi-DT conjugates were prepared using adipic acid dihydrazide (ADH) as the linker. All 5 lots showed consistency in their physical-chemical characteristics and final yields. These Vi-DT conjugates elicited significantly higher levels of IgG anti-Vi in young mice than those injected with Vi alone and induced booster response upon reinjection. This booster effect was absent if the Vi was substituting one of the two conjugate injections. Vi-DT was stable under repeated freeze-thaw (20 cycles). We plan to perform clinical evaluation of the safety and immunogenicity of Vi-DT when added to the infant combination vaccines.