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 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

doi:10.1016/j.celrep.2021.110143

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

Cell Rep. 2021 Dec 21;37(12):110143. doi: 10.1016/j.celrep.2021.110143. Epub 2021 Dec 8.

Authors

M Gordon Joyce¹, Wei-Hung Chen², Rajeshwer S Sankhala², Agnes Hajduczki², Paul V Thomas², Misook Choe², Elizabeth J Martinez², William C Chang², Caroline E Peterson², Elaine B Morrison³, Clayton Smith⁴, Rita E Chen⁵, Aslaa Ahmed⁶, Lindsay Wieczorek⁷, Alexander Anderson⁸, James Brett Case⁵, Yifan Li⁷, Therese Oertel⁸, Lorean Rosado⁷, Akshaya Ganesh⁸, Connor Whalen⁸, Joshua M Carmen³, Letzibeth Mendez-Rivera⁷, Christopher P Karch⁷, Neelakshi Gohain⁷, Zuzana Villar⁷, David McCurdy⁷, Zoltan Beck⁷, Jiae Kim⁷, Shikha Shrivastava⁷, Ousman Jobe⁷, Vincent Dussupt⁷, Sebastian Molnar⁷, Ursula Tran⁷, Chandrika B Kannadka⁷, Sandrine Soman⁶, Caitlin Kuklis⁶, Michelle Zemil⁷, Htet Khanh⁴, Weimin Wu⁴, Matthew A Cole⁹, Debra K Duso⁹, Larry W Kummer⁹, Tricia J Lang⁹, Shania E Muncil⁹, Jeffrey R Currier⁶, Shelly J Krebs⁷, Victoria R Polonis³, Saravanan Rajan¹⁰, Patrick M McTamney¹¹, Mark T Esser¹¹, William W Reiley⁹, Morgane Rolland⁷, Natalia de Val⁴, Michael S Diamond⁵, Gregory D Gromowski⁶, Gary R Matyas³, Mangala Rao³, Nelson L Michael¹², Kayvon Modjarrad¹³

Affiliations

¹ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. Electronic address: gjoyce@eidresearch.org.
² Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
³ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁴ Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
⁵ Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁶ Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁷ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁸ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Oak Ridge Institute of Science and Education, Oak Ridge, TN, USA.
⁹ Trudeau Institute, Inc., Saranac Lake, NY, USA.
¹⁰ Antibody Discovery and Protein Engineering (ADPE), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
¹¹ Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
¹² Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
¹³ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA. Electronic address: kayvon.modjarrad.civ@mail.mil.

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.

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.

Grants and funding

R01 AI157155/AI/NIAID NIH HHS/United States