Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine
- Author(s)
- Deliyannis, G; Gherardin, NA; Wong, CY; Grimley, SL; Cooney, JP; Redmond, SJ; Ellenberg, P; Davidson, KC; Mordant, FL; Smith, T; Gillard, M; Lopez, E; McAuley, J; Tan, CW; Wang, JJ; Zeng, W; Littlejohn, M; Zhou, R; Fuk-Woo Chan, J; Chen, ZW; Hartwig, AE; Bowen, R; Mackenzie, JM; Vincan, E; Torresi, J; Kedzierska, K; Pouton, CW; Gordon, TP; Wang, LF; Kent, SJ; Wheatley, AK; Lewin, SR; Subbarao, K; Chung, AW; Pellegrini, M; Munro, T; Nolan, T; Rockman, S; Jackson, DC; Purcell, DFJ; Godfrey, DI;
- Journal Title
- EBioMedicine
- Abstract
- 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.
- Publisher
- Elsevier
- Keywords
- Covid-19; Rbd; Receptor-binding domain; SARS-CoV-2; Vaccine
- Research Division(s)
- Infectious Diseases And Immune Defence
- PubMed ID
- 37148585
- Publisher's Version
- https://doi.org/10.1016/j.ebiom.2023.104574
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-06-07 03:10:38
Last Modified: 2023-06-07 03:38:44