TY - JOUR
T1 - Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine
AU - Deliyannis, Georgia
AU - Gherardin, Nicholas A.
AU - Wong, Chinn Yi
AU - Grimley, Samantha L.
AU - Cooney, James P.
AU - Redmond, Samuel J.
AU - Ellenberg, Paula
AU - Davidson, Kathryn C.
AU - Mordant, Francesca L.
AU - Smith, Tim
AU - Gillard, Marianne
AU - Lopez, Ester
AU - McAuley, Julie
AU - Tan, Chee Wah
AU - Wang, Jing J.
AU - Zeng, Weiguang
AU - Littlejohn, Mason
AU - Zhou, Runhong
AU - Chan, Jasper Fuk-Woo
AU - Chen, Zhi-wei
AU - Hartwig, Airn E.
AU - Bowen, Richard
AU - Mackenzie, Jason M.
AU - Vincan, Elizabeth
AU - Torresi, Joseph
AU - Kedzierska, Katherine
AU - Pouton, Colin W.
AU - Gordon, Tom P.
AU - Wang, Lin-fa
AU - Kent, Stephen J.
AU - Wheatley, Adam K.
AU - Lewin, Sharon R.
AU - Subbarao, Kanta
AU - Chung, Amy W.
AU - Pellegrini, Marc
AU - Munro, Trent
AU - Nolan, Terry
AU - Rockman, Steven
AU - Jackson, David C.
AU - Purcell, Damian F. J.
AU - Godfrey, Dale I.
PY - 2023/6
Y1 - 2023/6
N2 - Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace andscale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccinestability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverseevents associated with existing vaccines.Methods: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARSCoV-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.
AB - Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace andscale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccinestability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverseevents associated with existing vaccines.Methods: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARSCoV-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.
KW - SARS-CoV-2
KW - COVID-19
KW - Vaccine
KW - Receptor-binding domain
KW - RBD
UR - http://purl.org/au-research/grants/NHMRC/1113293
UR - http://www.scopus.com/inward/record.url?scp=85154564106&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2023.104574
DO - 10.1016/j.ebiom.2023.104574
M3 - Article
SN - 2352-3964
VL - 92
JO - EBioMedicine
JF - EBioMedicine
M1 - 104574
ER -
