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 PMID:32817941  

Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2.

Alexandra C Walls | Brooke Fiala | Alexandra Schäfer | Samuel Wrenn | Minh N Pham | Michael Murphy | Longping V Tse | Laila Shehata | Megan A O'Connor | Chengbo Chen | Mary Jane Navarro | Marcos C Miranda | Deleah Pettie | Rashmi Ravichandran | John C Kraft | Cassandra Ogohara | Anne Palser | Sara Chalk | E-Chiang Lee | Elizabeth Kepl | Cameron M Chow | Claire Sydeman | Edgar A Hodge | Brieann Brown | Jim T Fuller | Kenneth H Dinnon | Lisa E Gralinski | Sarah R Leist | Kendra L Gully | Thomas B Lewis | Miklos Guttman | Helen Y Chu | Kelly K Lee | Deborah H Fuller | Ralph S Baric | Paul Kellam | Lauren Carter | Marion Pepper | Timothy P Sheahan | David Veesler | Neil P King
bioRxiv : the preprint server for biology | 2020

A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, 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 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly 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 protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.

Pubmed ID: 32817941

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: HHSN272201700059C
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM099989
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM120553
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI106677

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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RRID:SCR_002891

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RRID:SCR_005375

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.

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laboratory mouse with name BALB/cAnNCrl from MGI.

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RRID:CVCL_0063

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