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Crystal structure of HLA-DRA*01:01/HLA-DRB1*04:01 in complex with c44H10 FabCrystal structure of HLA-DRA*01:01/HLA-DRB1*04:01 in complex with c44H10 Fab
Structural highlights
Publication Abstract from PubMedSubunit 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. Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses.,Kassardjian A, Sun E, Sookhoo J, Muthuraman K, Boligan KF, Kucharska I, Rujas E, Jetha A, Branch DR, Babiuk S, Barber B, Julien JP Cell Rep. 2023 Apr 25;42(4):112391. doi: 10.1016/j.celrep.2023.112391. Epub 2023 , Apr 3. PMID:37053069[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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