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TitleSARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.
Journal, issue, pagesbioRxiv, Year 2021
Publish dateMay 10, 2021
AuthorsM Gordon Joyce / Wei-Hung Chen / Rajeshwer S Sankhala / Agnes Hajduczki / Paul V Thomas / Misook Choe / William Chang / Caroline E Peterson / Elizabeth Martinez / Elaine B Morrison / Clayton Smith / Aslaa Ahmed / Lindsay Wieczorek / Alexander Anderson / Rita E Chen / James Brett Case / Yifan Li / Therese Oertel / Lorean Rosado / Akshaya Ganesh / Connor Whalen / Joshua M Carmen / Letzibeth Mendez-Rivera / Christopher Karch / Neelakshi Gohain / Zuzana Villar / David McCurdy / Zoltan Beck / Jiae Kim / Shikha Shrivastava / Ousman Jobe / Vincent Dussupt / Sebastian Molnar / Ursula Tran / Chandrika B Kannadka / 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 /
PubMed AbstractThe need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized ...The need for SARS-CoV-2 next-generation vaccines has been highlighted by the rise of variants of concern (VoC) and the long-term threat of other coronaviruses. Here, we designed and characterized four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of prefusion Spike (S), S1 and RBD. These immunogens induced robust S-binding, ACE2-inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2 in mice. A Spike-ferritin nanoparticle (SpFN) vaccine elicited neutralizing titers more than 20-fold higher than convalescent donor serum, following a single immunization, while RBD-Ferritin nanoparticle (RFN) immunogens elicited similar responses after two immunizations. Passive transfer of IgG purified from SpFN- or RFN-immunized mice protected K18-hACE2 transgenic mice from a lethal SARS-CoV-2 virus challenge. Furthermore, SpFN- and RFN-immunization elicited ACE2 blocking activity and neutralizing ID50 antibody titers >2,000 against SARS-CoV-1, along with high magnitude neutralizing titers against major VoC. These results provide design strategies for pan-coronavirus vaccine development.
HIGHLIGHTS: Iterative structure-based design of four Spike-domain Ferritin nanoparticle classes of immunogensSpFN-ALFQ and RFN-ALFQ immunization elicits potent neutralizing activity against SARS-CoV-2, variants of concern, and SARS-CoV-1Passively transferred IgG from immunized C57BL/6 mice protects K18-hACE2 mice from lethal SARS-CoV-2 challenge.
External linksbioRxiv / PubMed:34013273 / PubMed Central
MethodsEM (single particle)
Resolution30.0 - 40.0 Å
Structure data

EMDB-25448:
Negative-stain EM reconstruction of SpFN_1B-06-PL, a SARS-CoV-2 spike fused to H.pylori ferritin nanoparticle vaccine candidate
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-25449:
RFN_131, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Receptor-Binding Domain
Method: EM (single particle) / Resolution: 30.0 Å

EMDB-25450:
pCoV146, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Spike Receptor-Binding and N-Terminal Domains
Method: EM (single particle) / Resolution: 40.0 Å

EMDB-25451:
pCoV111, a Ferritin-based Nanoparticle Vaccine Candidate Displaying the SARS-CoV-2 Spike S1 Subunit
Method: EM (single particle) / Resolution: 30.0 Å

Source
  • Severe acute respiratory syndrome coronavirus 2

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