• Plos One · Jan 2012

    O:2-CRM(197) conjugates against Salmonella Paratyphi A.

    • Francesca Micoli, Simona Rondini, Massimiliano Gavini, Luisa Lanzilao, Donata Medaglini, Allan Saul, and Laura B Martin.
    • Novartis Vaccines Institute for Global Health, Siena, Italy. francesca.micoli@novartis.com
    • Plos One. 2012 Jan 1;7(11):e47039.

    AbstractEnteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A.

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