Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

Rajeshwer S Sankhala; Kerri G Lal; Jaime L Jensen; Vincent Dussupt; Letzibeth Mendez-Rivera; Hongjun Bai; Lindsay Wieczorek; Sandra V Mayer; Michelle Zemil; Danielle A Wagner; Samantha M Townsley; Agnes Hajduczki; William C Chang; Wei-Hung Chen; Gina C Donofrio; Ningbo Jian; Hannah A D King; Cynthia G Lorang; Elizabeth J Martinez; Phyllis A Rees; Caroline E Peterson; Fabian Schmidt; Tricia J Hart; Debra K Duso; Lawrence W Kummer; Sean P Casey; Jazmean K Williams; Shruthi Kannan; Bonnie M Slike; Lauren Smith; Isabella Swafford; Paul V Thomas; Ursula Tran; Jeffrey R Currier; Diane L Bolton; Edgar Davidson; Benjamin J Doranz; Theodora Hatziioannou; Paul D Bieniasz; Dominic Paquin-Proulx; William W Reiley; Morgane Rolland; Nancy J Sullivan; Sandhya Vasan; Natalie D Collins; Kayvon Modjarrad; Gregory D Gromowski; Victoria R Polonis; Nelson L Michael; Shelly J Krebs; M Gordon Joyce

doi:10.1038/s41467-023-44265-0

Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques

Nat Commun. 2024 Jan 3;15(1):200. doi: 10.1038/s41467-023-44265-0.

Authors

Rajeshwer S Sankhala^#^{1

2}, Kerri G Lal^#^{1

2}, Jaime L Jensen^{1

2}, Vincent Dussupt^{1

2

3}, Letzibeth Mendez-Rivera^{2

3}, Hongjun Bai^{1

2

3}, Lindsay Wieczorek^{2

3}, Sandra V Mayer^{1

2}, Michelle Zemil^{2

3}, Danielle A Wagner⁴, Samantha M Townsley^{2

3}, Agnes Hajduczki^{1

2}, William C Chang^{1

2}, Wei-Hung Chen^{1

2}, Gina C Donofrio^{2

3}, Ningbo Jian^{2

3}, Hannah A D King^{2

3}, Cynthia G Lorang⁴, Elizabeth J Martinez^{1

2}, Phyllis A Rees^{1

2}, Caroline E Peterson^{1

2}, Fabian Schmidt⁵, Tricia J Hart⁶, Debra K Duso⁶, Lawrence W Kummer⁶, Sean P Casey⁶, Jazmean K Williams⁷, Shruthi Kannan⁷, Bonnie M Slike^{2

3}, Lauren Smith^{2

3}, Isabella Swafford^{2

3}, Paul V Thomas^{1

2}, Ursula Tran^{2

3}, Jeffrey R Currier⁸, Diane L Bolton^{2

3}, Edgar Davidson⁷, Benjamin J Doranz⁷, Theodora Hatziioannou⁵, Paul D Bieniasz^{5

9}, Dominic Paquin-Proulx^{2

3}, William W Reiley⁶, Morgane Rolland^{1

2

3}, Nancy J Sullivan⁴, Sandhya Vasan^{1

2

3}, Natalie D Collins^{1

8}, Kayvon Modjarrad^{1

10}, Gregory D Gromowski⁸, Victoria R Polonis³, Nelson L Michael¹¹, Shelly J Krebs^{12

13}, M Gordon Joyce^{14

15}

Affiliations

¹ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
² 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 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ Laboratory of Retrovirology, The Rockefeller University, New York, NY, USA.
⁶ Trudeau Institute, Saranac Lake, NY, USA.
⁷ Integral Molecular, Philadelphia, PA, USA.
⁸ Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁹ Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.
¹⁰ Vaccine Research and Development, Pfizer, Pearl River, New York, NY, USA.
¹¹ Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
¹² Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA. skrebs@hivresearch.org.
¹³ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA. skrebs@hivresearch.org.
¹⁴ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA. gjoyce@eidresearch.org.
¹⁵ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA. gjoyce@eidresearch.org.

^# Contributed equally.

Abstract

The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

MeSH terms

Animals
Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Ferritins
Macaca mulatta
Mice
Nanoparticles*
Severe acute respiratory syndrome-related coronavirus*
Spike Glycoprotein, Coronavirus / genetics
Vaccination

Substances

Antibodies, Neutralizing
Antibodies, Viral
Antibodies, Monoclonal
COVID-19 Vaccines
Ferritins
Spike Glycoprotein, Coronavirus

Supplementary concepts

SARS-CoV-2 variants

Abstract

MeSH terms

Substances

Supplementary concepts

Grants and funding