Characterization of antigen adjuvant interactions in polyacrylate adjuvanted vaccines.

SPA09 is a polyacrylate-based clinical stage vaccine adjuvant that was found to exert a strong adjuvant effect on various vaccine antigens including recombinant cytomegalovirus glycoprotein B (CMV-gB). For the characterization of antigen-adjuvant interactions, which is a regulatory requirement and an important piece of information for the understanding of adjuvant mechanism of action, we developed a set of orthogonal techniques, comprising thermal analyses, biolayer interferometry and agarose gel migration assays. Here we apply these techniques to study the interaction between SPA09 and two recombinant proteins from the Sanofi new vaccine portfolio, CMV-gB and the Staphylococcus aureus chaperone protein, PrsA, that we used as model antigens. We believe that the techniques developed for this work could be useful to study the interactions between adjuvants and vaccine antigens in general and could be broadly applicable for the characterization of adjuvanted vaccine products.

An imidazole modified lipid confers enhanced mRNA-LNP stability and strong immunization properties in mice and non-human primates.

The mRNA vaccine technology has promising applications to fight infectious diseases as demonstrated by the licensing of two mRNA-based vaccines, Comirnaty® (Pfizer/BioNtech) and Spikevax® (Moderna), in the context of the Covid-19 crisis. Safe and effective delivery systems are essential to the performance of these vaccines and lipid nanoparticles (LNPs) able to entrap, protect and deliver the mRNA in vivo are considered by many as the current "best in class". Nevertheless, current mRNA/LNP vaccine technology has still some limitations, one of them being thermostability, as evidenced by the ultracold distribution chain required for the licensed vaccines. We found that the thermostability of mRNA/LNP, could be improved by a novel imidazole modified lipid, DOG-IM4, in combination with standard helper lipids. DOG-IM4 comprises an ionizable head group consisting of imidazole, a dioleoyl lipid tail and a short flexible polyoxyethylene spacer between the head and tail. Here we describe the synthesis of DOG-IM4 and show that DOG-IM4 LNPs confer strong immunization properties to influenza HA mRNA in mice and macaques and a remarkable stability to the encapsulated mRNA when stored liquid in phosphate buffered saline at 4 °C. We speculate the increased stability to result from some specific attributes of the lipid's imidazole head group.