tetano
Editor, Senior Moderator
Cell Rep
. 2023 Apr 3;42(4):112391.
doi: 10.1016/j.celrep.2023.112391. Online ahead of print.
Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses
Audrey Kassardjian[SUP] 1 [/SUP], Eric Sun[SUP] 1 [/SUP], Jamie Sookhoo[SUP] 2 [/SUP], Krithika Muthuraman[SUP] 3 [/SUP], Kayluz Frias Boligan[SUP] 4 [/SUP], Iga Kucharska[SUP] 5 [/SUP], Edurne Rujas[SUP] 6 [/SUP], Arif Jetha[SUP] 5 [/SUP], Donald R Branch[SUP] 7 [/SUP], Shawn Babiuk[SUP] 2 [/SUP], Brian Barber[SUP] 8 [/SUP], Jean-Philippe Julien[SUP] 9 [/SUP]
Affiliations
Abstract
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.
Keywords: CP: Immunology; MHC class II; SARS-CoV-2; adjuvants; antibodies; immunotargeting; vaccines.
. 2023 Apr 3;42(4):112391.
doi: 10.1016/j.celrep.2023.112391. Online ahead of print.
Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses
Audrey Kassardjian[SUP] 1 [/SUP], Eric Sun[SUP] 1 [/SUP], Jamie Sookhoo[SUP] 2 [/SUP], Krithika Muthuraman[SUP] 3 [/SUP], Kayluz Frias Boligan[SUP] 4 [/SUP], Iga Kucharska[SUP] 5 [/SUP], Edurne Rujas[SUP] 6 [/SUP], Arif Jetha[SUP] 5 [/SUP], Donald R Branch[SUP] 7 [/SUP], Shawn Babiuk[SUP] 2 [/SUP], Brian Barber[SUP] 8 [/SUP], Jean-Philippe Julien[SUP] 9 [/SUP]
Affiliations
- PMID: 37053069
- DOI: 10.1016/j.celrep.2023.112391
Abstract
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.
Keywords: CP: Immunology; MHC class II; SARS-CoV-2; adjuvants; antibodies; immunotargeting; vaccines.