A tractable covalent linker strategy for the production of immunogenic antigen-TLR7/8L bioconjugates.

Despite the ease of production and improved safety profiles of recombinant vaccines, the inherently low immunogenicity of unadjuvanted proteins remains an impediment to their widespread adoption. The covalent tethering of TLR agonists to antigenic proteins offers a unique approach to co-deliver both constituents to the same cell-enhancing vaccine efficacy while minimizing reactogenicity. However, the paucity of simple and effective linker chemistries continues to hamper progress. Here, we present a modular, PEG-based linker system compatible with even extremely lipophilic and challenging TLR7/8 agonists. To advance the field and address previous obstacles, we offer the most straightforward and antigen-preserving linker system to date. These antigen-adjuvant conjugates enhance antigen-specific immune responses in mice, demonstrating the power of our approach within the context of modern vaccinology.

Adsorption of fibrinogen on to polystyrene latex coated with the non-ionic surfactant, poloxamer 338.

We have measured the isothermal adsorption of 125I-fibrinogen on to polystyrene latex (PSL), which was prepared without surfactants, and on to PSL with an adsorbed coat of poloxamer 338 (an A-B-A block copolymer where A is poly(oxyethylene) and B is poly(oxypropylene]. The plateau adsorption of fibrinogen, at 310 K, was significantly lower on to latex coated with poloxamer 338. Previous studies have shown that poloxamer 338-coated PSL is cleared less avidly than uncoated PSL by cells of the mononuclear phagocytic system (MPS). Our findings are quantitative evidence in support of the theory that the uptake of colloids by the MPS can be related to the interfacial adsorption of opsonic proteins.