A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen

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Standard

A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. / 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; Kükrer, Başak; 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; Radošević, Katarina.

I: Science, Bind 349, Nr. 6254, 18.09.2015, s. 1301-1306.

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

Harvard

Impagliazzo, A, Milder, F, Kuipers, H, Wagner, MV, Zhu, X, Hoffman, RMB, van Meersbergen, R, Huizingh, J, Wanningen, P, Verspuij, J, de Man, M, Ding, Z, Apetri, A, Kükrer, B, Sneekes-Vriese, E, Tomkiewicz, D, Laursen, NS, Lee, PS, Zakrzewska, A, Dekking, L, Tolboom, J, Tettero, L, van Meerten, S, Yu, W, Koudstaal, W, Goudsmit, J, Ward, AB, Meijberg, W, Wilson, IA & Radošević, K 2015, 'A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen', Science, bind 349, nr. 6254, s. 1301-1306. https://doi.org/10.1126/science.aac7263

APA

Impagliazzo, A., Milder, F., Kuipers, H., Wagner, M. V., Zhu, X., Hoffman, R. M. B., van Meersbergen, R., Huizingh, J., Wanningen, P., Verspuij, J., de Man, M., Ding, Z., Apetri, A., Kükrer, B., Sneekes-Vriese, E., Tomkiewicz, D., Laursen, N. S., Lee, P. S., Zakrzewska, A., ... Radošević, K. (2015). A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science, 349(6254), 1301-1306. https://doi.org/10.1126/science.aac7263

CBE

Impagliazzo A, Milder F, Kuipers H, Wagner MV, Zhu X, Hoffman RMB, van Meersbergen R, Huizingh J, Wanningen P, Verspuij J, de Man M, Ding Z, Apetri A, Kükrer B, Sneekes-Vriese E, Tomkiewicz D, Laursen NS, Lee PS, Zakrzewska A, Dekking L, Tolboom J, Tettero L, van Meerten S, Yu W, Koudstaal W, Goudsmit J, Ward AB, Meijberg W, Wilson IA, Radošević K. 2015. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science. 349(6254):1301-1306. https://doi.org/10.1126/science.aac7263

MLA

Vancouver

Impagliazzo A, Milder F, Kuipers H, Wagner MV, Zhu X, Hoffman RMB o.a. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science. 2015 sep 18;349(6254):1301-1306. https://doi.org/10.1126/science.aac7263

Author

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 ; Kükrer, Başak ; 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 ; Radošević, Katarina. / A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. I: Science. 2015 ; Bind 349, Nr. 6254. s. 1301-1306.

Bibtex

@article{e08d0ac40f434f13992398a91d1a9ffd,
title = "A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen",
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.",
keywords = "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",
author = "Antonietta Impagliazzo and Fin Milder and Harmjan Kuipers and Wagner, {Michelle V} and Xueyong Zhu and Hoffman, {Ryan M B} and {van Meersbergen}, Ruud and Jeroen Huizingh and Patrick Wanningen and Johan Verspuij and {de Man}, Martijn and Zhaoqing Ding and Adrian Apetri and Ba{\c s}ak K{\"u}krer and Eveline Sneekes-Vriese and Danuta Tomkiewicz and Laursen, {Nick S} and Lee, {Peter S} and Anna Zakrzewska and Liesbeth Dekking and Jeroen Tolboom and Lisanne Tettero and {van Meerten}, Sander and Wenli Yu and Wouter Koudstaal and Jaap Goudsmit and Ward, {Andrew B} and Wim Meijberg and Wilson, {Ian A} and Katarina Rado{\v s}evi{\'c}",
note = "Copyright {\textcopyright} 2015, American Association for the Advancement of Science.",
year = "2015",
month = sep,
day = "18",
doi = "10.1126/science.aac7263",
language = "English",
volume = "349",
pages = "1301--1306",
journal = "Science",
issn = "0036-8075",
publisher = "AMER ASSOC ADVANCEMENT SCIENCE",
number = "6254",

}

RIS

TY - JOUR

T1 - A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen

AU - Impagliazzo, Antonietta

AU - Milder, Fin

AU - Kuipers, Harmjan

AU - Wagner, Michelle V

AU - Zhu, Xueyong

AU - Hoffman, Ryan M B

AU - van Meersbergen, Ruud

AU - Huizingh, Jeroen

AU - Wanningen, Patrick

AU - Verspuij, Johan

AU - de Man, Martijn

AU - Ding, Zhaoqing

AU - Apetri, Adrian

AU - Kükrer, Başak

AU - Sneekes-Vriese, Eveline

AU - Tomkiewicz, Danuta

AU - Laursen, Nick S

AU - Lee, Peter S

AU - Zakrzewska, Anna

AU - Dekking, Liesbeth

AU - Tolboom, Jeroen

AU - Tettero, Lisanne

AU - van Meerten, Sander

AU - Yu, Wenli

AU - Koudstaal, Wouter

AU - Goudsmit, Jaap

AU - Ward, Andrew B

AU - Meijberg, Wim

AU - Wilson, Ian A

AU - Radošević, Katarina

N1 - Copyright © 2015, American Association for the Advancement of Science.

PY - 2015/9/18

Y1 - 2015/9/18

N2 - 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.

AB - 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.

KW - Animals

KW - Antibodies, Neutralizing

KW - Antibodies, Viral

KW - Hemagglutinin Glycoproteins, Influenza Virus

KW - Humans

KW - Influenza A Virus, H1N1 Subtype

KW - Influenza A Virus, H5N1 Subtype

KW - Influenza Vaccines

KW - Influenza, Human

KW - Mice

KW - Protein Multimerization

KW - Protein Structure, Secondary

U2 - 10.1126/science.aac7263

DO - 10.1126/science.aac7263

M3 - Journal article

C2 - 26303961

VL - 349

SP - 1301

EP - 1306

JO - Science

JF - Science

SN - 0036-8075

IS - 6254

ER -