SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity

M. Gordon Joyce, Wei Hung Chen, Rajeshwer S. Sankhala, Agnes Hajduczki, Paul V. Thomas, Misook Choe, Elizabeth J. Martinez, William C. Chang, Caroline E. Peterson, Elaine B. Morrison, Clayton Smith, Rita E. Chen, Aslaa Ahmed, Lindsay Wieczorek, Alexander Anderson, James Brett Case, Yifan Li, Therese Oertel, Lorean Rosado, Akshaya GaneshConnor Whalen, Joshua M. Carmen, Letzibeth Mendez-Rivera, Christopher P. Karch, Neelakshi Gohain, Zuzana Villar, David McCurdy, Zoltan Beck, Jiae Kim, Shikha Shrivastava, Ousman Jobe, Vincent Dussupt, Sebastian Molnar, Ursula Tran, Chandrika B. Kannadka, Sandrine Soman, Caitlin Kuklis, Michelle Zemil, Htet Khanh, Weimin Wu, Matthew A. Cole, Debra K. Duso, Larry W. Kummer, Tricia J. Lang, Shania E. Muncil, Jeffrey R. Currier, Shelly J. Krebs, Victoria R. Polonis, Saravanan Rajan, Patrick M. McTamney, Mark T. Esser, William W. Reiley, Morgane Rolland, Natalia de Val, Michael S. Diamond, Gregory D. Gromowski, Gary R. Matyas, Mangala Rao, Nelson L. Michael, Kayvon Modjarrad

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of the prefusion SARS-CoV-2 spike (S), S1, and receptor-binding domain (RBD). These immunogens induce robust S binding, ACE2 inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2. A spike-ferritin nanoparticle (SpFN) vaccine elicits neutralizing titers (ID50 > 10,000) following a single immunization, whereas RBD-ferritin nanoparticle (RFN) immunogens elicit similar responses after two immunizations and also show durable and potent neutralization against circulating VoCs. Passive transfer of immunoglobulin G (IgG) purified from SpFN- or RFN-immunized mice protects K18-hACE2 transgenic mice from a lethal SARS-CoV-2 challenge. Furthermore, S-domain nanoparticle immunization elicits ACE2-blocking activity and ID50 neutralizing antibody titers >2,000 against SARS-CoV-1, highlighting the broad response elicited by these immunogens.

Original languageEnglish
Article number110143
JournalCell Reports
Volume37
Issue number12
DOIs
StatePublished - Dec 21 2021

Keywords

  • ALFQ
  • B.1.1.7
  • B.1.351
  • COVID-19
  • P.1
  • SARS-CoV-1
  • SARS-CoV-2
  • betacoronaviruses
  • ferritin nanoparticle
  • neutralizing antibodies
  • receptor-binding domain
  • spike
  • variants of concern

Fingerprint

Dive into the research topics of 'SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity'. Together they form a unique fingerprint.

Cite this