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  • Structure–Activity Relationship of a Series of Synthetic Lipopeptide Self-Adjuvanting Group A Streptococcal Vaccine Candidates

    Author(s)
    Abdel-Aal, Abu-Baker M.
    Batzloff, Michael R.
    Fujita, Yoshio
    Barozzi, Nadia
    Faria, Andres
    Simerska, Pavla
    Moyle, Peter M.
    Good, Michael F.
    Toth, Istvan
    Griffith University Author(s)
    Good, Michael F.
    Year published
    2008
    Metadata
    Show full item record
    Abstract
    The development of 16 self-adjuvanting group A streptococcal vaccine candidates, composed of (i) a universal helper T-cell epitope (P25), (ii) a target GAS B-cell epitope (J14), and (iii) a lipid moiety, is described. Systemic J14-specific IgG antibodies were detected following subcutaneous immunization of BALB/c (H-2d) mice with each construct without the need for an additional adjuvant. The effect of changing the order of P25, J14, and lipid moiety attachment or incorporation of P25 and J14 into a lipid-core peptide system on antibody titers was assessed. The point of lipid moiety attachment had the greatest influence on ...
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    The development of 16 self-adjuvanting group A streptococcal vaccine candidates, composed of (i) a universal helper T-cell epitope (P25), (ii) a target GAS B-cell epitope (J14), and (iii) a lipid moiety, is described. Systemic J14-specific IgG antibodies were detected following subcutaneous immunization of BALB/c (H-2d) mice with each construct without the need for an additional adjuvant. The effect of changing the order of P25, J14, and lipid moiety attachment or incorporation of P25 and J14 into a lipid-core peptide system on antibody titers was assessed. The point of lipid moiety attachment had the greatest influence on systemic J14-specific IgG antibody titers. Overall, the best vaccines featured a C-terminal lipid moiety, conjugated through a lysine residue to P25 at the N-terminus, and J14 on the lysine side chain.
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    Journal Title
    Journal of Medicinal Chemistry
    Volume
    51
    Issue
    1
    DOI
    https://doi.org/10.1021/jm701091d
    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
    Medicinal and Biomolecular Chemistry not elsewhere classified
    Medicinal and Biomolecular Chemistry
    Organic Chemistry
    Pharmacology and Pharmaceutical Sciences
    Publication URI
    http://hdl.handle.net/10072/39924
    Collection
    • Journal articles

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