Semisynthetic, self-adjuvanting vaccine development: Efficient, site-specific sortase A-mediated conjugation of Toll-like receptor 2 ligand FSL-1 to recombinant protein antigens under native conditions and application to a model group A streptococcal v...

What is it about?

This work developed a method to enable the site-specific and efficient attachment of immunostimulatory lipopeptide Toll-like receptor 2 agonists onto recombinant protein antigens, to generate potent vaccines. The work demonstrates the use of this system to protect against group A streptococcus infection in a murine model.

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Why is it important?

Purified proteins (subunit antigens) represent the majority of antigens reported in the literature for vaccine development. They however are not very immunogenic, and thus require the addition of delivery systems or immunostimulatory adjuvants to enable their use as vaccines. The ability to conjugate immunostimulatory adjuvants onto protein antigens increases their potency by targeting all vaccine components to the same cell, increasing potency, reducing the amount of vaccine required, and reducing adverse effects. The site-specific incorporation of lipopeptide adjuvants into recombinant proteins is complicated by their hydrophobicity and low aqueous solubility. However, such molecules have proven to be useful vaccines (e.g. Trumenba). These vaccines however incorporate an undesirable complex mixture of fatty acids owing to their recombinant origins. Our semisynthetic process is highly efficient, and generates a defined molecule incorporating only a single type of fatty acid. Which is desirable for the production and registration of new lipopeptide-based vaccines.