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Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s).
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067452/ https://www.ncbi.nlm.nih.gov/pubmed/37053069 http://dx.doi.org/10.1016/j.celrep.2023.112391 |
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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 |
author_facet | 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 |
author_sort | Kassardjian, Audrey |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10067452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Author(s). |
record_format | MEDLINE/PubMed |
spelling | pubmed-100674522023-04-03 Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses 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 Cell Rep Article 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. The Author(s). 2023-04-25 2023-04-03 /pmc/articles/PMC10067452/ /pubmed/37053069 http://dx.doi.org/10.1016/j.celrep.2023.112391 Text en © 2023 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article 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 Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses |
title | Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses |
title_full | Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses |
title_fullStr | Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses |
title_full_unstemmed | Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses |
title_short | Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses |
title_sort | modular adjuvant-free pan-hla-dr-immunotargeting subunit vaccine against sars-cov-2 elicits broad sarbecovirus-neutralizing antibody responses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067452/ https://www.ncbi.nlm.nih.gov/pubmed/37053069 http://dx.doi.org/10.1016/j.celrep.2023.112391 |
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