Summary A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic. Graphical Abstract Highlights • Two-component nanoparticle platform enabled rapid generation of SARS-CoV-2 vaccines • The RBD-nanoparticle vaccines elicit potent neutralizing antibody responses • Nanoparticle vaccine-elicited antibodies target multiple non-overlapping epitopes • The lead nanoparticle vaccine candidate is being manufactured for clinical trials Walls et al. describe a potential nanoparticle vaccine for COVID-19, made of a self-assembling protein nanoparticle displaying the SARS-CoV-2 receptor-binding domain in a highly immunogenic array reminiscent of the natural virus. Their nanoparticle vaccine candidate elicits a diverse, potent, and protective antibody response, including neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike ectodomain trimer.
【저자키워드】 SARS-CoV-2, Vaccine, Protein, RBD, nanoparticle, computational protein design, 【초록키워드】 clinical trial, antibody, SARS-CoV-2 pandemic, Antibody Response, mutations, risk, virus, SARS-CoV-2 vaccine, Antigen, Epitopes, stability, Receptor-binding domain, mice, immunogen, Respiratory disease, vaccine candidate, structure-based design, convalescent, utility, platform, Neutralizing antibody response, Neutralizing antibody titer, Protective, SARS-CoV-2 spike, RBDs, cGMP, Safe, domain, effort, trimer, immunogenic, ectodomain, human sera, lower dose, SARS-CoV-2-RBD, wall, susceptible, effective, highlight, robust, elicit, the RBD, induce, displaying, elicited, non-overlapping epitope, protective antibody response, the SARS-CoV-2, vaccine for COVID-19, 【제목키워드】 response, potent,