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

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...

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Published in:EBioMedicine 2023-06, Vol.92, p.104574-104574, Article 104574
Main Authors: Deliyannis, Georgia, Gherardin, Nicholas A., Wong, Chinn Yi, Grimley, Samantha L., Cooney, James P., Redmond, Samuel J., Ellenberg, Paula, Davidson, Kathryn C., Mordant, Francesca L., Smith, Tim, Gillard, Marianne, Lopez, Ester, McAuley, Julie, Tan, Chee Wah, Wang, Jing J., Zeng, Weiguang, Littlejohn, Mason, Zhou, Runhong, Fuk-Woo Chan, Jasper, Chen, Zhi-wei, Hartwig, Airn E., Bowen, Richard, Mackenzie, Jason M., Vincan, Elizabeth, Torresi, Joseph, Kedzierska, Katherine, Pouton, Colin W., Gordon, Tom P., Wang, Lin-fa, Kent, Stephen J., Wheatley, Adam K., Lewin, Sharon R., Subbarao, Kanta, Chung, Amy W., Pellegrini, Marc, Munro, Trent, Nolan, Terry, Rockman, Steven, Jackson, David C., Purcell, Damian F.J., Godfrey, Dale I.
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Animals
Antibodies, Neutralizing
Antibodies, Viral
Australia
Carrier Proteins
COVID-19
COVID-19 - prevention & control
COVID-19 Vaccines
Cricetinae
Humans
Mice
Protein Subunits
Rats
RBD
Receptor-binding domain
SARS-CoV-2
Vaccine
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Summary: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. 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. 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. 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. 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 Re
ISSN:2352-3964
2352-3964
DOI:10.1016/j.ebiom.2023.104574