6VRQ
Crystal structure of gl12A21 Fab in complex with anti-idiotypic iv12 Fab
Summary for 6VRQ
| Entry DOI | 10.2210/pdb6vrq/pdb |
| Descriptor | iv12 Fab Heavy Chain, iv12 Fab Light Chain, gl12A21 Fab Heavy Chain, ... (9 entities in total) |
| Functional Keywords | fab, complex, gl12a21, immune system, hiv, cd4-binding site, iv12 |
| Biological source | Mus musculus More |
| Total number of polymer chains | 4 |
| Total formula weight | 96639.65 |
| Authors | Aljedani, S.S.,Weidle, C.,Pancera, M. (deposition date: 2020-02-08, release date: 2021-02-17, Last modification date: 2024-11-06) |
| Primary citation | Seydoux, E.,Wan, Y.H.,Feng, J.,Wall, A.,Aljedani, S.,Homad, L.J.,MacCamy, A.J.,Weidle, C.,Gray, M.D.,Brumage, L.,Taylor, J.J.,Pancera, M.,Stamatatos, L.,McGuire, A.T. Development of a VRC01-class germline targeting immunogen derived from anti-idiotypic antibodies. Cell Rep, 35:109084-109084, 2021 Cited by PubMed Abstract: An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs). Broad and potent VRC01-class bNAbs have been isolated from multiple infected individuals, suggesting that they could be reproducibly elicited by vaccination. Several HIV-1 envelope-derived germline-targeting immunogens have been designed to engage naive VRC01-class precursor B cells. However, they also present off-target epitopes that could hinder development of VRC01-class bNAbs. We characterize a panel of anti-idiotypic monoclonal antibodies (ai-mAbs) raised against inferred-germline (iGL) VRC01-class antibodies. By leveraging binding, structural, and B cell sorting data, we engineered a bispecific molecule derived from two ai-mAbs; one specific for VRC01-class heavy chains and one specific for VRC01-class light chains. The bispecific molecule preferentially activates iGL-VRC01 B cells in vitro and induces specific antibody responses in a murine adoptive transfer model with a diverse polyclonal B cell repertoire. This molecule represents an alternative non-envelope-derived germline-targeting immunogen that can selectively activate VRC01-class precursors in vivo. PubMed: 33951425DOI: 10.1016/j.celrep.2021.109084 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.57 Å) |
Structure validation
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