Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology

Rory A Hills; Tiong Kit Tan; Alexander A Cohen; Jennifer R Keeffe; Anthony H Keeble; Priyanthi N P Gnanapragasam; Kaya N Storm; Michelle L Hill; Sai Liu; Javier Gilbert-Jaramillo; Madeeha Afzal; Amy Napier; William S James; Pamela J Bjorkman; Alain R Townsend; Mark Howarth

doi:10.1101/2023.02.24.529520

Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology

bioRxiv [Preprint]. 2023 Feb 24:2023.02.24.529520. doi: 10.1101/2023.02.24.529520.

Authors

Rory A Hills^{1

2}, Tiong Kit Tan³, Alexander A Cohen⁴, Jennifer R Keeffe⁴, Anthony H Keeble^{1

2}, Priyanthi N P Gnanapragasam⁴, Kaya N Storm⁴, Michelle L Hill⁵, Sai Liu⁵, Javier Gilbert-Jaramillo⁵, Madeeha Afzal⁵, Amy Napier⁵, William S James⁵, Pamela J Bjorkman⁴, Alain R Townsend^{3

6}, Mark Howarth^{1

2}

Affiliations

¹ Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
² Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.
³ MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DS, UK.
⁴ Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
⁵ James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
⁶ Centre for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, University of Oxford, Oxford, OX3 7BN, UK.

Abstract

Defending against future pandemics may require vaccine platforms that protect across a range of related pathogens. The presentation of multiple receptor-binding domains (RBDs) from evolutionarily-related viruses on a nanoparticle scaffold elicits a strong antibody response to conserved regions. Here we produce quartets of tandemly-linked RBDs from SARS-like betacoronaviruses coupled to the mi3 nanocage through a SpyTag/SpyCatcher spontaneous reaction. These Quartet Nanocages induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented on the vaccine. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increased the strength and breadth of an otherwise narrow immune response. Quartet Nanocages are a strategy with potential to confer heterotypic protection against emergent zoonotic coronavirus pathogens and facilitate proactive pandemic protection.

Keywords: Covid-19; bioconjugation; nanobiotechnology; outbreak pathogens; synthetic biology; zoonotic.

Publication types

Preprint