Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2
Индукция мощного ответа нейтрализующих антител с помощью разработанных белковых наночастичных вакцин против SARS-CoV-2
2020-10-31
SCID: 54.1/p4exmcg6
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SARS-CoV-2-RBD nanoparticle vaccineneutralizing antibody responsesreceptor-binding domainself-assembling protein nanoparticlesstructure-based vaccine design
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Abstract (AI)
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.
Key Findings
1
High nanoparticle yield and stability indicated strong scalability for manufacturing, enabling cGMP efforts toward clinical development.
2
Nanoparticle-elicited antibodies targeted multiple distinct epitopes, potentially reducing susceptibility to viral escape mutations.
3
RBD nanoparticles induced neutralizing antibody titers 10-fold higher than prefusion-stabilized spike while using a 5-fold lower dose.
4
Structure-based self-assembling protein nanoparticles displaying 60 SARS-CoV-2 spike RBDs elicited potent protective antibody responses in mice.
5
The antibodies showed a lower binding-to-neutralizing ratio than convalescent human sera, potentially minimizing vaccine-associated enhanced respiratory disease risk.
Research Object
Self-assembling protein nanoparticle vaccines displaying SARS-CoV-2 spike receptor-binding domains (RBDs)
Research Subject
The immunogenicity, neutralizing and protective antibody responses, epitope targeting, and manufacturability of the RBD nanoparticle vaccines
Publication Details
Publication Date
2020-10-31
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