Immunogenic fusion proteins induce neutralizing SARS-CoV-2 antibodies in the serum and milk of sheep

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dc.contributor.authorJacobson, Gregory M.en_NZ
dc.contributor.authorKraakman, Kirsty Leighen_NZ
dc.contributor.authorWallace, Oliviaen_NZ
dc.contributor.authorPan, Jolyn Tyn Tynen_NZ
dc.contributor.authorHennebry, Alexen_NZ
dc.contributor.authorSmolenski, Granten_NZ
dc.contributor.authorCursons, Raymond T.en_NZ
dc.contributor.authorHodgkinson, Steveen_NZ
dc.contributor.authorWilliamson, Adeleen_NZ
dc.contributor.authorKelton, Williamen_NZ
dc.coverage.spatialNetherlandsen_NZ
dc.date.accessioned2023-03-19T22:46:20Z
dc.date.available2023-03-19T22:46:20Z
dc.date.issued2023-06en_NZ
dc.description.abstractAntigen-specific polyclonal immunoglobulins derived from the serum, colostrum, or milk of immunized ruminant animals have potential as scalable therapeutics for the control of viral diseases including COVID-19. Here we show that the immunization of sheep with fusions of the SARS-CoV-2 receptor binding domain (RBD) to ovine IgG2a Fc domains promotes significantly higher levels of antigen-specific antibodies compared to native RBD or full-length spike antigens. This antibody population contained elevated levels of neutralizing antibodies that suppressed binding between the RBD and hACE2 receptors in vitro. A second immune-stimulating fusion candidate, Granulocyte-macrophage colony-stimulating factor (GM-CSF), induced high neutralizing responses in select animals but narrowly missed achieving significance. We further demonstrated that the antibodies induced by these fusion antigens were transferred into colostrum/milk and possessed cross-neutralizing activity against diverse SARS-CoV-2 variants. Our findings highlight a new pathway for recombinant antigen design in ruminant animals with applications in immune milk production and animal health.en_NZ
dc.format.mimetypeapplication/pdf
dc.identifier.doi10.1016/j.btre.2023.e00791en_NZ
dc.identifier.issn2215-017Xen_NZ
dc.identifier.urihttps://hdl.handle.net/10289/15622
dc.language.isoengen_NZ
dc.publisherElsevier B. V.
dc.relation.isPartOfBiotechnol Rep (Amst)en_NZ
dc.rights© 2023 The Author(s). This is an open-access article under the CC BY-NC-NDlicense.
dc.subjectAntigen designen_NZ
dc.subjectFc domainen_NZ
dc.subjectFc fusionen_NZ
dc.subjectImmune milken_NZ
dc.subjectSARS-CoV-2en_NZ
dc.titleImmunogenic fusion proteins induce neutralizing SARS-CoV-2 antibodies in the serum and milk of sheepen_NZ
dc.typeJournal Article
pubs.begin-pagee00791
pubs.elements-id305666
pubs.organisational-group/Waikato
pubs.organisational-group/Waikato/2026 PBRF
pubs.organisational-group/Waikato/DHECS
pubs.organisational-group/Waikato/DHECS/2026 PBRF - DHEC
pubs.organisational-group/Waikato/DHECS/SCHS
pubs.organisational-group/Waikato/DHECS/SHEA
pubs.organisational-group/Waikato/DHECS/SHEA/2026 PBRF - Te Huataki Waiora - School of Health
pubs.organisational-group/Waikato/PBRF Panel Groups
pubs.organisational-group/Waikato/PBRF Panel Groups/MEDPH - Medicine and Public Health
pubs.organisational-group/Waikato/Staff
pubs.publication-statusPublisheden_NZ
pubs.user.infoKelton, William (william.kelton@waikato.ac.nz)
pubs.user.infoCursons, Raymond (ray.cursons@waikato.ac.nz)
pubs.volume38en_NZ
uow.verification.statusverified
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