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

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

Cell reports (2021-12-18)
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 Ganesh, Connor 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
PMID34919799
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.