Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses
Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses
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Full item details
- creativework.keywords - en
- Vaccines, Subunit
- Vaccins sous-unitaires
- Vaccins contre la COVID-19
- Immunoglobulins
- Anticorps
- creativework.keywords - fr
- COVID-19 vaccines
- COVID-19 (Disease)
- COVID-19
- Adjuvants immunologiques
- Immunological adjuvants
- dc.contributor.author
- Kassardjian, Audrey
- Sun, Eric
- Sookhoo, Jamie
- Muthuraman, Krithika
- Boligan, Kayluz Frias
- Kucharska, Iga
- Rujas, Edurne
- Jetha, Arif
- Branch, Donald R.
- Babiuk, Shawn
- Barber, Brian
- Julien, Jean-Philippe
- dc.date.accepted
- 2023-03-29
- dc.date.accessioned
- 2024-08-19T13:26:21Z
- dc.date.available
- 2024-08-19T13:26:21Z
- dc.date.issued
- 2023-04-03
- dc.date.submitted
- 2022-11-09
- dc.description.abstract - en
- Subunit vaccines typically require co-administration with an adjuvant to elicit protective immunity, adding development hurdles that can impede rapid pandemic responses. To circumvent the need for adjuvant in a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) subunit vaccine, we engineer a thermostable immunotargeting vaccine (ITV) that leverages the pan-HLA-DR monoclonal antibody 44H10 to deliver the viral spike protein receptor-binding domain (RBD) to antigen-presenting cells. X-ray crystallography shows that 44H10 binds to a conserved epitope on HLA-DR, providing the basis for its broad HLA-DR reactivity. Adjuvant-free ITV immunization in rabbits and ferrets induces robust anti-RBD antibody responses that neutralize SARS-CoV-2 variants of concern and protect recipients from SARS-CoV-2 challenge. We demonstrate that the modular nature of the ITV scaffold with respect to helper T cell epitopes and diverse RBD antigens facilitates broad sarbecovirus neutralization. Our findings support anti-HLA-DR immunotargeting as an effective means to induce strong antibody responses to subunit antigens without requiring an adjuvant.
- dc.identifier.citation
- Kassardjian, A., Sun, E., Sookhoo, J., Muthuraman, K., Boligan, K. F., Kucharska, I., Rujas, E., Jetha, A., Branch, D. R., Babiuk, S., Barber, B., & Julien, J.-P. (2023). Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses. Cell Reports, 42(4), Article 112391. https://doi.org/10.1016/j.celrep.2023.112391
- dc.identifier.doi
- https://doi.org/10.1016/j.celrep.2023.112391
- dc.identifier.issn
- 2211-1247
- 2639-1856
- dc.identifier.uri
- https://open-science.canada.ca/handle/123456789/2848
- dc.language.iso
- en
- dc.publisher
- Elsevier
- dc.rights - en
- Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
- dc.rights - fr
- Creative Commons Attribution - Pas d'utilisation commerciale - Pas de modification 4.0 International (CC BY-NC-ND 4.0)
- dc.rights.openaccesslevel - en
- Gold
- dc.rights.openaccesslevel - fr
- Or
- dc.rights.uri - en
- https://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.rights.uri - fr
- https://creativecommons.org/licenses/by-nc-nd/4.0/deed.fr
- dc.subject - en
- Health and safety
- Science and technology
- dc.subject - fr
- Santé et sécurité
- Sciences et technologie
- dc.subject.en - en
- Health and safety
- Science and technology
- dc.subject.fr - fr
- Santé et sécurité
- Sciences et technologie
- dc.title - en
- Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses
- dc.type - en
- Article
- dc.type - fr
- Article
- local.acceptedmanuscript.articlenum
- 112391
- local.article.journalissue
- 4
- local.article.journaltitle
- Cell Reports
- local.article.journalvolume
- 42
- local.pagination
- 1-22
- local.peerreview - en
- Yes
- local.peerreview - fr
- Oui
- local.requestdoi
- No
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