Open AccessPhysical and Chemical Characterization and Immunologic Properties ofSalmonella entericaSerovar Typhi Capsular Polysaccharide-Diphtheria Toxoid Conjugates
Author(s) -
Changfa Cui,
Rodney Carbis,
So Jung An,
Han Byul Jang,
Cécil Czerkinsky,
Shousun C. Szu,
John D. Clemens
Publication year - 2010
Publication title -
clinical and vaccine immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.649
H-Index - 77
eISSN - 1556-6811
pISSN - 1556-679X
DOI - 10.1128/cvi.00266-09
Subject(s) - salmonella typhi , microbiology and biotechnology , diphtheria toxin , serotype , salmonella enterica , salmonella , diphtheria , toxoid , virology , biology , antigen , immunization , immunology , vaccination , bacteria , escherichia coli , toxin , biochemistry , genetics , gene
Typhoid fever remains a serious public health problem in 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 asSalmonella enterica serovar Typhi capsular Vi, did not confer protection against typhoid fever for this age group. Vi conjugate, prepared by binding Vi toPseudomonas aeruginosa recombinant exoprotein A (rEPA), induces protective levels of antibody at as young as 2 years old. Because of the lack of regulatory precedent for rEPA in licensing vaccines, we employed diphtheria toxoid (DT) as the carrier protein to accommodate 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 and chemical characteristics and final yields. These Vi-DT conjugates elicited levels of IgG anti-Vi in young mice significantly higher than those in mice injected with Vi alone and induced a booster response upon reinjection. This booster effect was absent if the Vi replaced 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.