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

• DOI: 10.1038/s41467-021-22867-w
• Publication Date: 2021-05-11T10:04:54Z
• Authors: Linling He; Anshul Chaudhary; Xiaohe Lin; Cindy Sou; Tanwee Alkutkar; Sonu Kumar; Timothy Ngo; Ezra Kosviner; Gabriel Ozorowski; Robyn L. Stanfield; Andrew B. Ward; Ian A. Wilson; Jiang Zhu
• Keywords: Component (thermodynamics); Ebolavirus; Ebola vaccine

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 contribution of stalk heptad repeat 1-C (HR1 C ) regions to GP metastability. Specific HR1 modifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations exert more complex effect on thermostability. Crystal structures are determined validate two rationally designed GPΔmuc trimers their unliganded state. We then display modified reengineered protein nanoparticles that encapsulate layer locking domains (LD) cluster helper T-cell epitopes. In mice rabbits, elicit cross-ebolavirus NAbs, as well non-NAbs enhance pseudovirus infection. Repertoire sequencing reveals quantitative profiles vaccine-induced B-cell responses. This study demonstrates promising strategy filoviruses, such EBOV, based stabilization nanoparticle display.