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  • Development of a Liposaccharide-Based Delivery System and Its Application to the Design of Group A Streptococcal Vaccines

    Author(s)
    Simerska, Pavla
    Abdel-Aal, Abu-Baker M.
    Fujita, Yoshio
    Moyle, Peter M.
    McGeary, Ross P.
    Batzloff, Michael R.
    Olive, Colleen
    Good, Michael Francis
    Toth, Istvan
    Griffith University Author(s)
    Batzloff, Michael R.
    Year published
    2008
    Metadata
    Show full item record
    Abstract
    Group A streptococcus (GAS) is associated with many human diseases, ranging in severity from benign to life-threatening. A promising strategy for developing vaccines against GAS involves the use of carbohydrates as carriers for peptide antigens. This study describes the optimized synthesis of d-glucose and d-galactose derived carriers, bearing an adipate linker and four tert-butoxycarbonyl protected aminopropyl groups. Prophylactic GAS vaccine candidates were synthesized by conjugating multiple copies of a single GAS M protein derived peptide antigen (either J8 or J14) onto the carbohydrate carriers. These antigens contain ...
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    Group A streptococcus (GAS) is associated with many human diseases, ranging in severity from benign to life-threatening. A promising strategy for developing vaccines against GAS involves the use of carbohydrates as carriers for peptide antigens. This study describes the optimized synthesis of d-glucose and d-galactose derived carriers, bearing an adipate linker and four tert-butoxycarbonyl protected aminopropyl groups. Prophylactic GAS vaccine candidates were synthesized by conjugating multiple copies of a single GAS M protein derived peptide antigen (either J8 or J14) onto the carbohydrate carriers. These antigens contain peptide sequences, which are highly conserved and offer the potential to prevent infections caused by up to 70% of GAS strains. Lipophilic amino acids were also conjugated to the d-glucose anomeric carbon to produce a self-adjuvanting liposaccharide vaccine. High serum IgG antibody titers against each of the incorporated peptide epitopes were detected following subcutaneous immunization of B10.BR (H-2k) mice with the liposaccharide vaccine candidates.
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    Journal Title
    Journal of Medicinal Chemistry
    Volume
    51
    Issue
    5
    DOI
    https://doi.org/10.1021/jm701410p
    Copyright Statement
    Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.
    Subject
    Infectious Agents
    Medicinal and Biomolecular Chemistry
    Organic Chemistry
    Pharmacology and Pharmaceutical Sciences
    Publication URI
    http://hdl.handle.net/10072/39958.1
    Collection
    • Journal articles

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