Download MendeleyA stable trimeric influenza hemagglutinin stem as a broadly protective immunogen.
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.(2015) Science 349: 1301-1306
- PubMed: 26303961
- DOI: https://doi.org/10.1126/science.aac7263
- Primary Citation of Related Structures:
5CJQ, 5CJS - 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.
Organizational Affiliation:
Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, 2301 CA Leiden, Netherlands. aimpagli@its.jnj.com wilson@scripps.edu.
