| Literature DB >> 26303961 |
Antonietta Impagliazzo1, Fin Milder2, Harmjan Kuipers2, Michelle V Wagner3, Xueyong Zhu4, Ryan M B Hoffman4, Ruud van Meersbergen2, Jeroen Huizingh2, Patrick Wanningen2, Johan Verspuij2, Martijn de Man2, Zhaoqing Ding3, Adrian Apetri2, Başak Kükrer2, Eveline Sneekes-Vriese2, Danuta Tomkiewicz2, Nick S Laursen4, Peter S Lee4, Anna Zakrzewska2, Liesbeth Dekking2, Jeroen Tolboom2, Lisanne Tettero2, Sander van Meerten2, Wenli Yu4, Wouter Koudstaal2, Jaap Goudsmit2, Andrew B Ward4, Wim Meijberg2, Ian A Wilson5, Katarina Radošević2.
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.Entities:
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Year: 2015 PMID： 26303961 DOI： 10.1126/science.aac7263
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728