Nature Biotechnol. http://doi.org/8z3 (2015)

There are a number of design considerations when developing nanoparticle-based vaccines with optimal immunogenicity. Previous studies have shown how the effectiveness of a protein or peptide antigen can be enhanced through co-administration of an appropriate adjuvant. Geoffrey Lynn and colleagues now present a systematic study of how the physicochemical properties of polymer-linked adjuvants can dictate their in vivo pharmacokinetic profiles. They firstly generated a combinatorial library of chemically distinct polymers bearing Toll-like receptor agonist adjuvants in varying densities. They found that those polymers that were more susceptible to aggregation displayed significantly improved biodistributions and immune responses following in vivo administration. Taking advantage of these findings, they then succeeded in developing a stimuli-sensitive polymer, bearing these same adjuvants as well as antigenic peptides, which aggregates into an active immunogenic nanoparticle at physiological temperatures. These findings serve to demonstrate how the judicious selection of a polymeric carrier can significantly enhance the efficacy of antigen/adjuvant combination vaccines.