A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Antonietta Impagliazzo, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Fin Milder, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Harmjan Kuipers, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Michelle V Wagner, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, USA
  • Xueyong Zhu, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, USA
  • Ryan M B Hoffman, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, USA
  • Ruud van Meersbergen, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Jeroen Huizingh, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Patrick Wanningen, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Johan Verspuij, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Martijn de Man, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Zhaoqing Ding, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, USA
  • Adrian Apetri, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Başak Kükrer, Danmark
  • Eveline Sneekes-Vriese, Danmark
  • Danuta Tomkiewicz, Danmark
  • Nick S Laursen
  • Peter S Lee, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, USA
  • Anna Zakrzewska, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Liesbeth Dekking, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Jeroen Tolboom, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Lisanne Tettero, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Sander van Meerten, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Wenli Yu, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, USA
  • Wouter Koudstaal, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Jaap Goudsmit, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Andrew B Ward, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, USA
  • Wim Meijberg, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland
  • Ian A Wilson, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, USA
  • Katarina Radošević, Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Holland

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.

OriginalsprogEngelsk
TidsskriftScience
Vol/bind349
Nummer6254
Sider (fra-til)1301-1306
Antal sider6
ISSN0036-8075
DOI
StatusUdgivet - 18 sep. 2015

    Forskningsområder

  • Animals, Antibodies, Neutralizing, Antibodies, Viral, Hemagglutinin Glycoproteins, Influenza Virus, Humans, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H5N1 Subtype, Influenza Vaccines, Influenza, Human, Mice, Protein Multimerization, Protein Structure, Secondary

Se relationer på Aarhus Universitet Citationsformater

ID: 94295584