8VS8

Crystal structure of ADI-19425 Fab in complex with anti-idiotypic 1D3 Fab

Summary for 8VS8

• Entry DOI: 10.2210/pdb8vs8/pdb
• Descriptor: ADI-19425 Heavy Chain, ADI-19425 Light Chain, 1D3 Light Chain, ... (5 entities in total)
• Functional Keywords: rsv, antibody, anti-idiotype, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 32
• Total formula weight: 757465.02

Authors

Kher, G.,Homad, L.J.,McGuire, A.T.,Pancera, M. (deposition date: 2024-01-23, release date: 2024-09-18, Last modification date: 2026-04-01)

Primary citation

Scharffenberger, S.C.,Wan, Y.H.,Homad, L.J.,Kher, G.,Haynes, A.M.,Poudel, B.,Sinha, I.R.,Aldridge, N.,Pai, A.,Bibby, M.,Chhan, C.B.,Davis, A.R.,Moodie, Z.,Palacio, M.B.,Escolano, A.,McElrath, M.J.,Boonyaratanakornkit, J.,Pancera, M.,McGuire, A.T.
Targeting RSV-neutralizing B cell receptors with anti-idiotypic antibodies.
Cell Rep, 43:114811-114811, 2024

PubMed Abstract: Respiratory syncytial virus (RSV) causes lower respiratory tract infections with significant morbidity and mortality at the extremes of age. Vaccines based on the viral fusion protein are approved for adults over 60, but infant protection relies on passive immunity via antibody transfer or maternal vaccination. An infant vaccine that rapidly elicits protective antibodies would fulfill a critical unmet need. Antibodies arising from the VH3-21/VL1-40 gene pairing can neutralize RSV without the need for affinity maturation, making them attractive to target through vaccination. Here, we develop an anti-idiotypic monoclonal antibody (ai-mAb) immunogen that is specific for unmutated VH3-21/VL1-40 B cell receptors (BCRs). The ai-mAb efficiently engages B cells with bona fide target BCRs and does not activate off-target non-neutralizing B cells, unlike recombinant pre-fusion (preF) protein used in current RSV vaccines. These results establish proof of concept for using an ai-mAb-derived vaccine to target B cells hardwired to produce RSV-neutralizing antibodies.

PubMed: 39383036
DOI: 10.1016/j.celrep.2024.114811

Experimental method

X-RAY DIFFRACTION (2.67 Å)