A Divalent Chikungunya and Zika Nanovaccine with Thermostable Self‐Assembly Multivalent Scaffold LS‐SUMO

Abstract The convergence strategies of antigenic subunits and synthetic nanoparticle scaffold platform improve the vaccine production efficiency and enhance vaccine‐induced immunogenicity. Selecting the appropriate nanoparticle scaffold is crucial to controlling target antigens immunologically. Lumazine synthase (LS) is an attractive candidate for a vaccine display system due to its thermostability, modification tolerance, and morphological plasticity. Here, the first development of a multivalent thermostable scaffold, LS‐SUMO (SUMO, small ubiquitin‐likemodifier), and a divalent nanovaccine covalently conjugated with Chikungunya virus E2 and Zika virus EDIII antigens, is reported. Compared with antigen monomers, LS‐SUMO nanoparticle vaccines elicit a higher humoral response and neutralizing antibodies against both antigen targets in mouse sera. Mice immunized with LS‐SUMO conjugates produce CD4 + T cell‐mediated Th2‐biased responses and promote humoral immunity. Importantly, LS‐SUMO conjugates possess equivalent humoral immunogenicity after heat treatment. Taken together, LS‐SUMO is a powerful biotargeting nanoplatform with high‐yield production, thermal stability and opens a new avenue for multivalent presentation of various antigens.