Publication Date:
2015-08-26
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Impagliazzo, Antonietta -- Milder, Fin -- Kuipers, Harmjan -- Wagner, Michelle V -- Zhu, Xueyong -- Hoffman, Ryan M B -- van Meersbergen, Ruud -- Huizingh, Jeroen -- Wanningen, Patrick -- Verspuij, Johan -- de Man, Martijn -- Ding, Zhaoqing -- Apetri, Adrian -- Kukrer, Basak -- Sneekes-Vriese, Eveline -- Tomkiewicz, Danuta -- Laursen, Nick S -- Lee, Peter S -- Zakrzewska, Anna -- Dekking, Liesbeth -- Tolboom, Jeroen -- Tettero, Lisanne -- van Meerten, Sander -- Yu, Wenli -- Koudstaal, Wouter -- Goudsmit, Jaap -- Ward, Andrew B -- Meijberg, Wim -- Wilson, Ian A -- Radosevic, Katarina -- P41GM103393/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1301-6. doi: 10.1126/science.aac7263. Epub 2015 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, 2301 CA Leiden, Netherlands. aimpagli@its.jnj.com wilson@scripps.edu. ; Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Archimedesweg 4-6, 2301 CA Leiden, Netherlands. ; Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, 3210 Merryfield Row, San Diego, CA 92121, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. aimpagli@its.jnj.com wilson@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26303961" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies, Neutralizing/immunology
;
Antibodies, Viral/immunology
;
Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/*immunology
;
Humans
;
Influenza A Virus, H1N1 Subtype/*immunology
;
Influenza A Virus, H5N1 Subtype/*immunology
;
Influenza Vaccines/*immunology
;
Influenza, Human/*prevention & control
;
Mice
;
Protein Multimerization
;
Protein Structure, Secondary
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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