8D01

The domain-swaped dimer of the HIV-1 CD4bs targeting antibody 21N13

Summary for 8D01

• Entry DOI: 10.2210/pdb8d01/pdb
• Descriptor: 21N13 Fab heavy chain, 21N13 Fab light chain (3 entities in total)
• Functional Keywords: hiv-1 cd4bs antibody, domain swap dimer, viral protein-immune system complex, viral protein/immune system
• Biological source: Macaca mulatta (Rhesus monkey); More
• Total number of polymer chains: 4
• Total formula weight: 95560.21

Authors

Xian, Y.,Wilson, I.A. (deposition date: 2022-05-25, release date: 2023-12-13, Last modification date: 2025-07-02)

Primary citation

Caniels, T.G.,Medina-Ramirez, M.,Zhang, S.,Kratochvil, S.,Xian, Y.,Koo, J.H.,Derking, R.,Samsel, J.,van Schooten, J.,Pecetta, S.,Lamperti, E.,Yuan, M.,Carrasco, M.R.,Del Moral Sanchez, I.,Allen, J.D.,Bouhuijs, J.H.,Yasmeen, A.,Ketas, T.J.,Snitselaar, J.L.,Bijl, T.P.L.,Martin, I.C.,Torres, J.L.,Cupo, A.,Shirreff, L.,Rogers, K.,Mason, R.D.,Roederer, M.,Greene, K.M.,Gao, H.,Silva, C.M.,Baken, I.J.L.,Tian, M.,Alt, F.W.,Pulendran, B.,Seaman, M.S.,Crispin, M.,van Gils, M.J.,Montefiori, D.C.,McDermott, A.B.,Villinger, F.J.,Koup, R.A.,Moore, J.P.,Klasse, P.J.,Ozorowski, G.,Batista, F.D.,Wilson, I.A.,Ward, A.B.,Sanders, R.W.
Germline-targeting HIV vaccination induces neutralizing antibodies to the CD4 binding site.
Sci Immunol, 9:eadk9550-eadk9550, 2024

PubMed Abstract: Eliciting potent and broadly neutralizing antibodies (bnAbs) is a major goal in HIV-1 vaccine development. Here, we describe how germline-targeting immunogen BG505 SOSIP germline trimer 1.1 (GT1.1), generated through structure-based design, engages a diverse range of VRC01-class bnAb precursors. A single immunization with GT1.1 expands CD4 binding site (CD4bs)-specific VRC01-class B cells in knock-in mice and drives VRC01-class maturation. In nonhuman primates (NHPs), GT1.1 primes CD4bs-specific neutralizing serum responses. Selected monoclonal antibodies (mAbs) isolated from GT1.1-immunized NHPs neutralize fully glycosylated BG505 virus. Two mAbs, 12C11 and 21N13, neutralize subsets of diverse heterologous neutralization-resistant viruses. High-resolution structures revealed that 21N13 targets the same conserved residues in the CD4bs as VRC01-class and CH235-class bnAbs despite its low sequence similarity (~40%), whereas mAb 12C11 binds predominantly through its heavy chain complementarity-determining region 3. These preclinical data underpin the ongoing evaluation of GT1.1 in a phase 1 clinical trial in healthy volunteers.

PubMed: 39213338
DOI: 10.1126/sciimmunol.adk9550

Experimental method

X-RAY DIFFRACTION (2.46 Å)