EBioMedicine (Jun 2023)

Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccineResearch in context

  • Georgia Deliyannis,
  • Nicholas A. Gherardin,
  • Chinn Yi Wong,
  • Samantha L. Grimley,
  • James P. Cooney,
  • Samuel J. Redmond,
  • Paula Ellenberg,
  • Kathryn C. Davidson,
  • Francesca L. Mordant,
  • Tim Smith,
  • Marianne Gillard,
  • Ester Lopez,
  • Julie McAuley,
  • Chee Wah Tan,
  • Jing J. Wang,
  • Weiguang Zeng,
  • Mason Littlejohn,
  • Runhong Zhou,
  • Jasper Fuk-Woo Chan,
  • Zhi-wei Chen,
  • Airn E. Hartwig,
  • Richard Bowen,
  • Jason M. Mackenzie,
  • Elizabeth Vincan,
  • Joseph Torresi,
  • Katherine Kedzierska,
  • Colin W. Pouton,
  • Tom P. Gordon,
  • Lin-fa Wang,
  • Stephen J. Kent,
  • Adam K. Wheatley,
  • Sharon R. Lewin,
  • Kanta Subbarao,
  • Amy W. Chung,
  • Marc Pellegrini,
  • Trent Munro,
  • Terry Nolan,
  • Steven Rockman,
  • David C. Jackson,
  • Damian F.J. Purcell,
  • Dale I. Godfrey

Journal volume & issue
Vol. 92
p. 104574

Abstract

Read online

Summary: Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. Methods: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid α-Galactosylceramide, or MF59® squalene oil-in-water adjuvant, using mice, rats and hamsters. We also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the immuno-evasive beta variant (N501Y, E484K, K417N). These vaccines were also tested as a heterologous third dose booster in mice, following priming with whole spike vaccine. Findings: Each formulation of the RBD-Fc vaccines drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. The ‘beta variant’ RBD vaccine, combined with MF59® adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a heterologous third dose booster, the RBD-Fc vaccines combined with MF59® increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1, BA.2 and BA.5. Interpretation: These results demonstrated that an RBD-Fc protein subunit/MF59® adjuvanted vaccine can induce high levels of broadly reactive nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial. Funding: This work was supported by grants from the Medical Research Future Fund (MRFF) (2005846), The Jack Ma Foundation, National Health and Medical Research Council of Australia (NHMRC; 1113293) and Singapore National Medical Research Council (MOH-COVID19RF-003). Individual researchers were supported by an NHMRC Senior Principal Research Fellowship (1117766), NHMRC Investigator Awards (2008913 and 1173871), Australian Research Council Discovery Early Career Research Award (ARC DECRA; DE210100705) and philanthropic awards from IFM investors and the A2 Milk Company.

Keywords