Engineering a Rugged Nanoscaffold To Enhance Plug-and-Display Vaccination

By Theodora U. J. Bruun, Anne-Marie C. Andersson, S. Draper, M. Howarth. 2018

264 citations recorded by the source corpus.

Nanoscale organization is crucial to stimulating an immune response. Using self-assembling proteins as multimerization platforms provides a safe and immunogenic system to vaccinate against otherwise weakly immunogenic antigens. Such multimerization platforms are generally based on icosahedral viruses and have led to vaccines given to millions of people. It is unclear whether synthetic protein nanoassemblies would show similar potency. Here we take the computationally designed porous dodecahedral i301 60-mer and rationally engineer this particle, giving a mutated i301 (mi3) with improved particle uniformity and stability. To simplify the conjugation of this nanoparticle, we employ a SpyCatcher fusion of mi3, such that an antigen of interest linked to the SpyTag peptide can spontaneously couple through isopeptide bond formation (Plug-and-Display). SpyCatcher-mi3 expressed solubly to high yields in Escherichia coli, giving more than 10-fold greater yield than a comparable phage-derived icosahedral nanoparticle, SpyCatcher-AP205. SpyCatcher-mi3 nanoparticles showed high stability to temperature, freeze–thaw, lyophilization, and storage over time. We demonstrate approximately 95% efficiency coupling to different transmission-blocking and blood-stage malaria antigens. Plasmodium falciparum CyRPA was conjugated to SpyCatcher-mi3 nanoparticles and elicited a high avidity antibody response, comparable to phage-derived virus-like particles despite their higher valency and RNA cargo. The simple production, precise derivatization, and exceptional ruggedness of this nanoscaffold should facilitate broad application for nanobiotechnology and vaccine development.

Subfields: Ecology, Molecular Biology, Radiology, Nuclear Medicine and Imaging

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Citations in the corpus

Title: Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice (2020, unknown): “Two versions of each RBD expression vector were made: one including a C-terminal hexahistidine tag (G-HHHHHH) and SpyTag003 (RGVPHIVMVDAYKRYK) (43) (for coupling to SpyCatcher003-mi3) and one with only a hexahistidine tag (for ELISAs).”
Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers (2020, methodology): “Because VLPs conjugated with more than two different HAs tended to precipitate out of solution, we switched to the SpyCatcher-mi3 NP platform, which is similarly immunogenic as the AP205 platform, but has been shown to exhibit improved yields, stability, and uniformity [19].”