Single-component multilayered self-assembling nanoparticles presenting rationally designed glycoprotein trimers as Ebola virus vaccines.

ABSTRACT: Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate the contribution of the stalk and heptad repeat 1-C (HR1_C) regions to GP metastability. Specific stalk and HR1_C modifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations of HR1_C exert a more complex effect on thermostability. Crystal structures are determined to validate two rationally designed GPΔmuc trimers in their unliganded state. We then display a modified GPΔmuc trimer on reengineered protein nanoparticles that encapsulate a layer of locking domains (LD) and a cluster of helper T-cell epitopes. In mice and rabbits, GP trimers and nanoparticles elicit cross-ebolav

SUBMITTER: He L 

PROVIDER: S-EPMC8113551 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature