Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

Hannah A D King; M Gordon Joyce; Ines Lakhal-Naouar; Aslaa Ahmed; Camila Macedo Cincotta; Caroline Subra; Kristina K Peachman; Holly R Hack; Rita E Chen; Paul V Thomas; Wei-Hung Chen; Rajeshwer S Sankhala; Agnes Hajduczki; Elizabeth J Martinez; Caroline E Peterson; William C Chang; Misook Choe; Clayton Smith; Jarrett A Headley; Hanne A Elyard; Anthony Cook; Alexander Anderson; Kathryn McGuckin Wuertz; Ming Dong; Isabella Swafford; James B Case; Jeffrey R Currier; Kerri G Lal; Mihret F Amare; Vincent Dussupt; Sebastian Molnar; Sharon P Daye; Xiankun Zeng; Erica K Barkei; Kendra Alfson; Hilary M Staples; Ricardo Carrion; Shelly J Krebs; Dominic Paquin-Proulx; Nicos Karasavvas; Victoria R Polonis; Linda L Jagodzinski; Sandhya Vasan; Paul T Scott; Yaoxing Huang; Manoj S Nair; David D Ho; Natalia de Val; Michael S Diamond; Mark G Lewis; Mangala Rao; Gary R Matyas; Gregory D Gromowski; Sheila A Peel; Nelson L Michael; Kayvon Modjarrad; Diane L Bolton

doi:10.1073/pnas.2106433118

Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

Proc Natl Acad Sci U S A. 2021 Sep 21;118(38):e2106433118. doi: 10.1073/pnas.2106433118.

Authors

Hannah A D King^{1

2

3}, M Gordon Joyce^{2

3}, Ines Lakhal-Naouar^{3

4}, Aslaa Ahmed⁵, Camila Macedo Cincotta^{3

4}, Caroline Subra^{1

2

3}, Kristina K Peachman⁴, Holly R Hack^{3

4}, Rita E Chen^{6

7}, Paul V Thomas^{2

3}, Wei-Hung Chen^{2

3}, Rajeshwer S Sankhala^{2

3}, Agnes Hajduczki^{2

3}, Elizabeth J Martinez^{2

3}, Caroline E Peterson^{2

3}, William C Chang^{2

3}, Misook Choe^{2

3}, Clayton Smith⁸, Jarrett A Headley^{2

3}, Hanne A Elyard⁹, Anthony Cook⁹, Alexander Anderson^{1

2

3}, Kathryn McGuckin Wuertz¹, Ming Dong^{1

2

3}, Isabella Swafford^{1

2

3}, James B Case⁶, Jeffrey R Currier⁵, Kerri G Lal^{1

2

3}, Mihret F Amare^{2

3}, Vincent Dussupt^{1

2

3}, Sebastian Molnar^{1

2

3}, Sharon P Daye¹⁰, Xiankun Zeng¹¹, Erica K Barkei¹², Kendra Alfson¹³, Hilary M Staples¹³, Ricardo Carrion¹³, Shelly J Krebs^{1

2

3}, Dominic Paquin-Proulx^{1

2

3}, Nicos Karasavvas^{3

4}, Victoria R Polonis¹, Linda L Jagodzinski⁴, Sandhya Vasan^{1

2

3}, Paul T Scott², Yaoxing Huang¹⁴, Manoj S Nair¹⁴, David D Ho¹⁴, Natalia de Val⁸, Michael S Diamond^{6

7

15}, Mark G Lewis⁹, Mangala Rao¹, Gary R Matyas¹, Gregory D Gromowski⁵, Sheila A Peel⁴, Nelson L Michael¹⁰, Kayvon Modjarrad¹⁶, Diane L Bolton^{17

2

3}

Affiliations

¹ US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
² Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
³ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817.
⁴ Diagnostics and Countermeasures Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
⁵ Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
⁶ Department of Medicine, Washington University, St. Louis, MO 63130.
⁷ Department of Pathology & Immunology, Washington University, St. Louis, MO 63130.
⁸ Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702.
⁹ BIOQUAL, Inc., Rockville, MD 20850.
¹⁰ Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
¹¹ Division of Pathology, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702.
¹² Veterinary Pathology Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
¹³ Disease Intervention and Prevention, Texas Biomedical Research Institute, San Antonio, TX 78227.
¹⁴ Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032.
¹⁵ Department of Molecular Microbiology, Washington University, St. Louis, MO 63130.
¹⁶ Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910; kmodjarrad@eidresearch.org dbolton@hivresearch.org.
¹⁷ US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910; kmodjarrad@eidresearch.org dbolton@hivresearch.org.

Abstract

Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 µg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV-like Sarbecovirus vaccine development.

Keywords: SARS-CoV-2; adjuvant; macaque; nanoparticle; vaccine.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adjuvants, Immunologic / administration & dosage
Animals
Antibodies, Neutralizing / biosynthesis
Antibodies, Neutralizing / immunology
Antibodies, Viral / biosynthesis
Antibodies, Viral / immunology
COVID-19 / prevention & control
COVID-19 / virology*
COVID-19 Vaccines / administration & dosage*
COVID-19 Vaccines / immunology
Ferritins / chemistry
Macaca mulatta / immunology*
Nanoparticles / chemistry*
Receptors, Virus / metabolism*
SARS-CoV-2 / immunology*
SARS-CoV-2 / metabolism
T-Lymphocytes / immunology

Substances

Adjuvants, Immunologic
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Receptors, Virus
Ferritins

Abstract

Publication types

MeSH terms

Substances

Grants and funding