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

Author:

Dalvie Neil C.12ORCID,Tostanoski Lisa H.3ORCID,Rodriguez-Aponte Sergio A.24ORCID,Kaur Kawaljit5ORCID,Bajoria Sakshi5ORCID,Kumru Ozan S.5ORCID,Martinot Amanda J.36ORCID,Chandrashekar Abishek3ORCID,McMahan Katherine3ORCID,Mercado Noe B.3ORCID,Yu Jingyou3ORCID,Chang Aiquan37ORCID,Giffin Victoria M.3ORCID,Nampanya Felix3ORCID,Patel Shivani3ORCID,Bowman Lesley8ORCID,Naranjo Christopher A.2,Yun Dongsoo2,Flinchbaugh Zach9,Pessaint Laurent9ORCID,Brown Renita9,Velasco Jason9,Teow Elyse9,Cook Anthony9,Andersen Hanne9ORCID,Lewis Mark G.9ORCID,Camp Danielle L.2,Silverman Judith Maxwell10ORCID,Nagar Gaurav S.11,Rao Harish D.11,Lothe Rakesh R.11,Chandrasekharan Rahul11,Rajurkar Meghraj P.11,Shaligram Umesh S.11,Kleanthous Harry12ORCID,Joshi Sangeeta B.5,Volkin David B.5,Biswas Sumi813,Love J. Christopher1214ORCID,Barouch Dan H.371415ORCID

Affiliation:

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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