9MK4

Crystal structure of the VRC01-class antibody 12A01 derived from GT1.1 vaccination

Summary for 9MK4

• Entry DOI: 10.2210/pdb9mk4/pdb
• Related: 9MIC 9MID 9MIF 9MJ3 9MJ6 9MJC 9MJD 9MJI
• Descriptor: 12A01 Fab heavy chain, 12A01 Fab light chain (2 entities in total)
• Functional Keywords: hiv-1, germline-targeting vaccination, cd4bs mab, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 94853.67

Authors

Agrawal, S.,Wilson, I.A. (deposition date: 2024-12-16, release date: 2025-05-28, Last modification date: 2025-06-04)

Primary citation

Caniels, T.G.,Prabhakaran, M.,Ozorowski, G.,MacPhee, K.J.,Wu, W.,van der Straten, K.,Agrawal, S.,Derking, R.,Reiss, E.I.M.M.,Millard, K.,Turroja, M.,Desrosiers, A.,Bethony, J.,Malkin, E.,Liesdek, M.H.,van der Veen, A.,Klouwens, M.,Snitselaar, J.L.,Bouhuijs, J.H.,Bronson, R.,Jean-Baptiste, J.,Gajjala, S.,Rikhtegaran Tehrani, Z.,Benner, A.,Ramaswami, M.,Duff, M.O.,Liu, Y.W.,Sato, A.H.,Kim, J.Y.,Baken, I.J.L.,Mendes Silva, C.,Bijl, T.P.L.,van Rijswijk, J.,Burger, J.A.,Cupo, A.,Yasmeen, A.,Phulera, S.,Lee, W.H.,Randall Jr., K.N.,Zhang, S.,Corcoran, M.M.,Regadas, I.,Sullivan, A.C.,Brown, D.M.,Bohl, J.A.,Greene, K.M.,Gao, H.,Yates, N.L.,Sawant, S.,Prins, J.M.,Kootstra, N.A.,Kaminsky, S.M.,Barin, B.,Rahaman, F.,Meller, M.,Philiponis, V.,Laufer, D.S.,Lombardo, A.,Mwoga, L.,Shotorbani, S.,Holman, D.,Koup, R.A.,Klasse, P.J.,Karlsson Hedestam, G.B.,Tomaras, G.D.,van Gils, M.J.,Montefiori, D.C.,McDermott, A.B.,Hyrien, O.,Moore, J.P.,Wilson, I.A.,Ward, A.B.,Diemert, D.J.,de Bree, G.J.,Andrews, S.F.,Caskey, M.,Sanders, R.W.
Precise targeting of HIV broadly neutralizing antibody precursors in humans.
Science, :eadv5572-eadv5572, 2025

PubMed Abstract: A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, that target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design.

PubMed: 40373114
DOI: 10.1126/science.adv5572

Experimental method

X-RAY DIFFRACTION (3 Å)