SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques

Neil C Dalvie; Lisa H Tostanoski; Sergio A Rodriguez-Aponte; Kawaljit Kaur; Sakshi Bajoria; Ozan S Kumru; Amanda J Martinot; Abishek Chandrashekar; Katherine McMahan; Noe B Mercado; Jingyou Yu; Aiquan Chang; Victoria M Giffin; Felix Nampanya; Shivani Patel; Lesley Bowman; Christopher A Naranjo; Dongsoo Yun; Zach Flinchbaugh; Laurent Pessaint; Renita Brown; Jason Velasco; Elyse Teow; Anthony Cook; Hanne Andersen; Mark G Lewis; Danielle L Camp; Judith Maxwell Silverman; Gaurav S Nagar; Harish D Rao; Rakesh R Lothe; Rahul Chandrasekharan; Meghraj P Rajurkar; Umesh S Shaligram; Harry Kleanthous; Sangeeta B Joshi; David B Volkin; Sumi Biswas; J Christopher Love; Dan H Barouch

doi:10.1126/sciadv.abl6015

SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques

Sci Adv. 2022 Mar 18;8(11):eabl6015. doi: 10.1126/sciadv.abl6015. Epub 2022 Mar 16.

Authors

Neil C Dalvie^{1

2}, Lisa H Tostanoski³, Sergio A Rodriguez-Aponte^{2

4}, Kawaljit Kaur⁵, Sakshi Bajoria⁵, Ozan S Kumru⁵, Amanda J Martinot^{3

6}, Abishek Chandrashekar³, Katherine McMahan³, Noe B Mercado³, Jingyou Yu³, Aiquan Chang^{3

7}, Victoria M Giffin³, Felix Nampanya³, Shivani Patel³, Lesley Bowman⁸, Christopher A Naranjo², Dongsoo Yun², Zach Flinchbaugh⁹, Laurent Pessaint⁹, Renita Brown⁹, Jason Velasco⁹, Elyse Teow⁹, Anthony Cook⁹, Hanne Andersen⁹, Mark G Lewis⁹, Danielle L Camp², Judith Maxwell Silverman¹⁰, Gaurav S Nagar¹¹, Harish D Rao¹¹, Rakesh R Lothe¹¹, Rahul Chandrasekharan¹¹, Meghraj P Rajurkar¹¹, Umesh S Shaligram¹¹, Harry Kleanthous¹², Sangeeta B Joshi⁵, David B Volkin⁵, Sumi Biswas^{8

13}, J Christopher Love^{1

2

14}, Dan H Barouch^{3

7

14

15}

Affiliations

¹ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
⁴ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁵ Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS 66047, USA.
⁶ Departments of Infectious Diseases and Global Health and Comparative Pathobiology, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA.
⁷ Harvard Medical School, Boston, MA 02115, USA.
⁸ SpyBiotech Limited, Oxford Business Park North, Oxford OX4 2JZ, UK.
⁹ Bioqual, Rockville, MD 20852, USA.
¹⁰ Bill and Melinda Gates Medical Research Institute, Cambridge, MA 02139, USA.
¹¹ Serum Institute of India Pvt. Ltd., Pune, India.
¹² Bill and Melinda Gates Foundation, Seattle, WA 98109, USA.
¹³ The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK.
¹⁴ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
¹⁵ Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.

Abstract

Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain-hepatitis B surface antigen virus-like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>10⁴) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (~3.4 log₁₀) and nasal mucosa (~2.9 log₁₀) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses.

Abstract

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