8EUQ

Crystal structure of HLA-DRA*01:01/HLA-DRB1*04:01 in complex with c44H10 Fab

Summary for 8EUQ

• Entry DOI: 10.2210/pdb8euq/pdb
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, c44H10 Fab light chain, Hemagglutinin HA1 chain,HLA class II histocompatibility antigen DR beta chain, ... (7 entities in total)
• Functional Keywords: mhc class ii, hla-dr, antibody, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 192812.35

Authors

Kassardjian, A.,Julien, J.-P. (deposition date: 2022-10-19, release date: 2023-04-19, Last modification date: 2024-10-09)

Primary 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.
Modular adjuvant-free pan-HLA-DR-immunotargeting subunit vaccine against SARS-CoV-2 elicits broad sarbecovirus-neutralizing antibody responses.
Cell Rep, 42:112391-112391, 2023

PubMed 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.

PubMed: 37053069
DOI: 10.1016/j.celrep.2023.112391

Experimental method

X-RAY DIFFRACTION (3.09 Å)