5CJQ

Crystal structure of a trimeric influenza hemagglutinin stem in complex with an broadly neutralizing antibody CR9114

Summary for 5CJQ

• Entry DOI: 10.2210/pdb5cjq/pdb
• Related: 5CJS
• Descriptor: CR9114 light chain, CR9114 heavy chain, Designed influenza hemagglutinin stem #4900, HA1, ... (4 entities in total)
• Functional Keywords: hemagglutinin, trimer, influenza, immunogen, monoclonal, antibody, neutralizing, influenza vaccine, glycoprotein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 76192.67

Authors

Zhu, X.,Wilson, I.A. (deposition date: 2015-07-14, release date: 2015-09-09, Last modification date: 2024-11-13)

Primary citation

Impagliazzo, A.,Milder, F.,Kuipers, H.,Wagner, M.V.,Zhu, X.,Hoffman, R.M.,van Meersbergen, R.,Huizingh, J.,Wanningen, P.,Verspuij, J.,de Man, M.,Ding, Z.,Apetri, A.,Kukrer, B.,Sneekes-Vriese, E.,Tomkiewicz, D.,Laursen, N.S.,Lee, P.S.,Zakrzewska, A.,Dekking, L.,Tolboom, J.,Tettero, L.,van Meerten, S.,Yu, W.,Koudstaal, W.,Goudsmit, J.,Ward, A.B.,Meijberg, W.,Wilson, I.A.,Radosevic, K.
A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen.
Science, 349:1301-1306, 2015

PubMed Abstract: The identification of human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem revitalized hopes of developing a universal influenza vaccine. Using a rational design and library approach, we engineered stable HA stem antigens ("mini-HAs") based on an H1 subtype sequence. Our most advanced candidate exhibits structural and bnAb binding properties comparable to those of full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever after sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bound a wide range of HAs, competed with human bnAbs for HA stem binding, neutralized H5N1 viruses, and mediated antibody-dependent effector activity. These results represent a proof of concept for the design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses.

PubMed: 26303961
DOI: 10.1126/science.aac7263

Experimental method

X-RAY DIFFRACTION (3.6 Å)